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Sample records for abnormal brain tissue

  1. Brain tissue- and region-specific abnormalities on volumetric MRI scans in 21 patients with Bardet-Biedl syndrome (BBS)

    PubMed Central

    2011-01-01

    Background Bardet-Biedl syndrome (BBS) is a heterogeneous human disorder inherited in an autosomal recessive pattern, and characterized by the primary findings of obesity, polydactyly, hypogonadism, and learning and behavioural problems. BBS mouse models have a neuroanatomical phenotype consisting of third and lateral ventriculomegaly, thinning of the cerebral cortex, and reduction in the size of the corpus striatum and hippocampus. These abnormalities raise the question of whether humans with BBS have a characteristic morphologic brain phenotype. Further, although behavioral, developmental, neurological and motor defects have been noted in patients with BBS, to date, there are limited reports of brain findings in BBS. The present study represents the largest systematic evaluation for the presence of structural brain malformations and/or progressive changes, which may contribute to these functional problems. Methods A case-control study of 21 patients, most aged 13-35 years, except for 2 patients aged 4 and 8 years, who were diagnosed with BBS by clinical criteria and genetic analysis of known BBS genes, and were evaluated by qualitative and volumetric brain MRI scans. Healthy controls were matched 3:1 by age, sex and race. Statistical analysis was performed using SAS language with SAS STAT procedures. Results All 21 patients with BBS were found to have statistically significant region- and tissue-specific patterns of brain abnormalities. There was 1) normal intracranial volume; 2) reduced white matter in all regions of the brain, but most in the occipital region; 3) preserved gray matter volume, with increased cerebral cortex volume in only the occipital lobe; 4) reduced gray matter in the subcortical regions of the brain, including the caudate, putamen and thalamus, but not in the cerebellum; and 5) increased cerebrospinal fluid volume. Conclusions There are distinct and characteristic abnormalities in tissue- and region- specific volumes of the brain in patients

  2. Schizophrenia and abnormal brain network hubs

    PubMed Central

    Rubinov, Mikail; Bullmore, Ed.

    2013-01-01

    Schizophrenia is a heterogeneous psychiatric disorder of unknown cause or characteristic pathology. Clinical neuroscientists increasingly postulate that schizophrenia is a disorder of brain network organization. In this article we discuss the conceptual framework of this dysconnection hypothesis, describe the predominant methodological paradigm for testing this hypothesis, and review recent evidence for disruption of central/hub brain regions, as a promising example of this hypothesis. We summarize studies of brain hubs in large-scale structural and functional brain networks and find strong evidence for network abnormalities of prefrontal hubs, and moderate evidence for network abnormalities of limbic, temporal, and parietal hubs. Future studies are needed to differentiate network dysfunction from previously observed gray- and white-matter abnormalities of these hubs, and to link endogenous network dysfunction phenotypes with perceptual, behavioral, and cognitive clinical phenotypes of schizophrenia. PMID:24174905

  3. Spectromicroscopy of Brain Tissue

    NASA Astrophysics Data System (ADS)

    Frazer, Bradley; Cannara, Rachel; Gilbert, Benjamin; Destasio, Gelsomina; Ogg, Mandy; Gough, Kathy

    2001-03-01

    X-ray PhotoElectron Emission Microscopy (X-PEEM) was originally developed for studying the surface microchemistry of materials science specimens. It has then evolved into a valuable tool to investigate the magnetic properties of materials and the microchemistry of cells and tissues. We used the MEPHISTO X-PEEM instrument, installed at the UW-Synchrotron Radiation Center to detect trace concentrations of non-physiological elements in senile brain tissue specimens. These tissues contain a large number of plaques, in which all the compounds and elements that the brain does not need are disposed and stored. We hypothesized that plaques should contain elements, such as Si, B, and Al which are very abundant on the Earth crust but absent from healthy tissues. We verified this hypothesis with MEPHISTO and found evidence of Si and B, and suspect Al. We also found a higher than normal concentration of Fe.

  4. Developmental disruptions underlying brain abnormalities in ciliopathies

    PubMed Central

    Guo, Jiami; Higginbotham, Holden; Li, Jingjun; Nichols, Jackie; Hirt, Josua; Ghukasyan, Vladimir; Anton, E.S.

    2015-01-01

    Primary cilia are essential conveyors of signals underlying major cell functions. Cerebral cortical progenitors and neurons have a primary cilium. The significance of cilia function for brain development and function is evident in the plethora of developmental brain disorders associated with human ciliopathies. Nevertheless, the role of primary cilia function in corticogenesis remains largely unknown. Here we delineate the functions of primary cilia in the construction of cerebral cortex and their relevance to ciliopathies, using an shRNA library targeting ciliopathy genes known to cause brain disorders, but whose roles in brain development are unclear. We used the library to query how ciliopathy genes affect distinct stages of mouse cortical development, in particular neural progenitor development, neuronal migration, neuronal differentiation and early neuronal connectivity. Our results define the developmental functions of ciliopathy genes and delineate disrupted developmental events that are integrally related to the emergence of brain abnormalities in ciliopathies. PMID:26206566

  5. Volume estimation of brain abnormalities in MRI data

    NASA Astrophysics Data System (ADS)

    Suprijadi, Pratama, S. H.; Haryanto, F.

    2014-02-01

    The abnormality of brain tissue always becomes a crucial issue in medical field. This medical condition can be recognized through segmentation of certain region from medical images obtained from MRI dataset. Image processing is one of computational methods which very helpful to analyze the MRI data. In this study, combination of segmentation and rendering image were used to isolate tumor and stroke. Two methods of thresholding were employed to segment the abnormality occurrence, followed by filtering to reduce non-abnormality area. Each MRI image is labeled and then used for volume estimations of tumor and stroke-attacked area. The algorithms are shown to be successful in isolating tumor and stroke in MRI images, based on thresholding parameter and stated detection accuracy.

  6. Clinical Correlation between Perverted Nystagmus and Brain MRI Abnormal Findings

    PubMed Central

    Han, Won-Gue; Yoon, Hee-Chul; Kim, Tae-Min; Rah, Yoon Chan

    2016-01-01

    Background and Objectives To analyze the clinical correlation between perverted nystagmus and brain magnetic resonance imaging (MRI) abnormal findings and to evaluate whether perverted nystagmus is clinically significant results of brain abnormal lesions or not. Subjects and Methods We performed medical charts review from January 2008 to July 2014, retrospectively. Patients who were suspected central originated vertigo at Frenzel goggles test were included among patients who visited our hospital. To investigate the correlation with nystagmus suspected central originated vertigo and brain MRI abnormal findings, we confirmed whether performing brain MRI or not. Then we exclude that patients not performed brain MRI. Results The number of patients with perverted nystagmus was 15, upbeating was 1 and down-beating was 14. Among these patients, 5 patients have brain MRI abnormal findings. However, 2 patients with MRI abnormal findings were not associated correctly with perverted nystagmus and only 3 patients with perverted nystagmus were considered central originated vertigo and further evaluation and treatment was performed by the department of neurology. Conclusions Perverted nystagmus was considered to the abnormalities at brain lesions, especially cerebellum, but neurologic symptoms and further evaluation were needed for exact diagnosis of central originated vertigo. PMID:27626081

  7. Abnormal brain scan with subacute extradural haematomas

    PubMed Central

    Morley, J. Barrie; Langford, Keith H.

    1970-01-01

    Four patients are described with proven subacute extradural haematomas, each with an abnormal cerebral scan of diagnostic assistance. A possible mechanism of production of the subacute extradural haematoma is discussed, and appears to be similar to the mechanism involved in the subacute subdural haematoma. The means by which the abnormal scan results in such cases is also examined, from which it appears that non-specific meningeal membrane inflammatory reaction surrounding the haematoma is significant. Images PMID:5478950

  8. Photoacoustic Measurements in Brain Tissue

    SciTech Connect

    Kasili, P.M.; Mobley, J.; Vo-Dinh, T.

    1999-09-19

    In this work, we develop and evaluate the photoacoustic technique for recording spectra of white and gray mammalian brain tissues. In addition to the experimental work, we also discuss the geometric aspects of photoacoustic signal generation using collimated light. Spectra constructed from the peak-to-peak amplitude of the photoacoustic waveforms indicate differences in the two tissue types at wavelengths between 620 and 695 nm. The potential of the technique for non-invasive diagnosis is discussed.

  9. Brief Report: Brain Mechanisms in Autism: Functional and Structural Abnormalities.

    ERIC Educational Resources Information Center

    Minshew, Nancy J.

    1996-01-01

    This paper summarizes results of research on functional and structural abnormalities of the brain in autism. The current concept of causation is seen to involve multiple biologic levels. A consistent profile of brain function and dysfunction across methods has been found and specific neuropathologic findings have been found; but some research…

  10. Structural brain abnormalities in cervical dystonia

    PubMed Central

    2013-01-01

    Background Idiopathic cervical dystonia is characterized by involuntary spasms, tremors or jerks. It is not restricted to a disturbance in the basal ganglia system because non-conventional voxel-based MRI morphometry (VBM) and diffusion tensor imaging (DTI) have detected numerous regional changes in the brains of patients. In this study scans of 24 patients with cervical dystonia and 24 age-and sex-matched controls were analysed using VBM, DTI and magnetization transfer imaging (MTI) using a voxel-based approach and a region-of-interest analysis. Results were correlated with UDRS, TWSTRS and disease duration. Results We found structural alterations in the basal ganglia; thalamus; motor cortex; premotor cortex; frontal, temporal and parietal cortices; visual system; cerebellum and brainstem of the patients with dystonia. Conclusions Cervical dystonia is a multisystem disease involving several networks such as the motor, sensory and visual systems. PMID:24131497

  11. Genetic abnormality predicts benefit for a rare brain tumor

    Cancer.gov

    A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

  12. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    ERIC Educational Resources Information Center

    Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

    2008-01-01

    Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

  13. Robotic palpation and mechanical property characterization for abnormal tissue localization.

    PubMed

    Ahn, Bummo; Kim, Yeongjin; Oh, Cheol Kyu; Kim, Jung

    2012-09-01

    Palpation is an intuitive examination procedure in which the kinesthetic and tactile sensations of the physician are used. Although it has been widely used to detect and localize diseased tissues in many clinical fields, the procedure is subjective and dependent on the experience of the individual physician. Palpation results and biomechanics-based mechanical property characterization are possible solutions that can enable the acquisition of objective and quantitative information on abnormal tissue localization during diagnosis and surgery. This paper presents an integrated approach for robotic palpation combined with biomechanical soft tissue characterization. In particular, we propose a new palpation method that is inspired by the actual finger motions that occur during palpation procedures. To validate the proposed method, robotic palpation experiments on silicone soft tissue phantoms with embedded hard inclusions were performed and the force responses of the phantoms were measured using a robotic palpation system. Furthermore, we carried out a numerical analysis, simulating the experiments and estimating the objective and quantitative properties of the tissues. The results indicate that the proposed approach can differentiate diseased tissue from normal tissue and can characterize the mechanical information of diseased tissue, which means that this method can be applied as a means of abnormality localization to diagnose prostate cancers. PMID:22772733

  14. Connectivity and functional profiling of abnormal brain structures in pedophilia

    PubMed Central

    Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-01-01

    Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  15. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    PubMed

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

  16. Brain abnormality segmentation based on l1-norm minimization

    NASA Astrophysics Data System (ADS)

    Zeng, Ke; Erus, Guray; Tanwar, Manoj; Davatzikos, Christos

    2014-03-01

    We present a method that uses sparse representations to model the inter-individual variability of healthy anatomy from a limited number of normal medical images. Abnormalities in MR images are then defined as deviations from the normal variation. More precisely, we model an abnormal (pathological) signal y as the superposition of a normal part ~y that can be sparsely represented under an example-based dictionary, and an abnormal part r. Motivated by a dense error correction scheme recently proposed for sparse signal recovery, we use l1- norm minimization to separate ~y and r. We extend the existing framework, which was mainly used on robust face recognition in a discriminative setting, to address challenges of brain image analysis, particularly the high dimensionality and low sample size problem. The dictionary is constructed from local image patches extracted from training images aligned using smooth transformations, together with minor perturbations of those patches. A multi-scale sliding-window scheme is applied to capture anatomical variations ranging from fine and localized to coarser and more global. The statistical significance of the abnormality term r is obtained by comparison to its empirical distribution through cross-validation, and is used to assign an abnormality score to each voxel. In our validation experiments the method is applied for segmenting abnormalities on 2-D slices of FLAIR images, and we obtain segmentation results consistent with the expert-defined masks.

  17. Volumetric brain abnormalities in polysubstance use disorder patients

    PubMed Central

    Noyan, Cemal Onur; Kose, Samet; Nurmedov, Serdar; Metin, Baris; Darcin, Aslı Enez; Dilbaz, Nesrin

    2016-01-01

    Aim Polysubstance users represent the largest group of patients seeking treatment at addiction and rehabilitation clinics in Turkey. There is little knowledge about the structural brain abnormalities seen in polysubstance users. This study was conducted to examine the structural brain differences between polysubstance use disorder patients and healthy control subjects using voxel-based morphometry. Methods Forty-six male polysubstance use disorder patients in the early abstinence period and 30 healthy male controls underwent structural magnetic resonance imaging scans. Voxel-based morphometry analysis was performed to examine gray matter (GM) abnormality differences. Results Polysubstance use disorder patients displayed significantly smaller GM volume in the thalamus, temporal pole, superior frontal gyrus, cerebellum, gyrus rectus, occipital lobe, anterior cingulate cortex, superior temporal gyrus, and postcentral gyrus. Conclusion A widespread and smaller GM volume has been found at different regions of the frontal, temporal, occipital, and parietal lobes, cerebellum, and anterior cingulate cortex in polysubstance users. PMID:27358566

  18. Early Blood Gas Abnormalities and the Preterm Brain

    PubMed Central

    Leviton, Alan; Allred, Elizabeth; Kuban, Karl C. K.; Dammann, Olaf; O'Shea, T. Michael; Hirtz, Deborah; Schreiber, Michael D.; Paneth, Nigel

    2010-01-01

    The authors explored associations between blood gas abnormalities in more than 1,000 preterm infants during the first postnatal days and indicators of neonatal brain damage. During 2002–2004, women delivering infants before 28 weeks’ gestation at one of 14 participating institutions in 5 US states were asked to enroll in the study. The authors compared infants with blood gas values in the highest or lowest quintile for gestational age and postnatal day (extreme value) on at least 1 of the first 3 postnatal days with the remainder of the subjects, with separate analyses for blood gas abnormalities on multiple days and for partial pressure of oxygen in the alveolar gas of <35. Outcomes analyzed were ventriculomegaly and an echolucent lesion on an ultrasound scan in the neonatal intensive care unit, and cerebral palsy, microcephaly, and a low score on a Bayley Scale of Infant Development at 24 months. Every blood gas derangement (hypoxemia, hyperoxemia, hypocapnia, hypercapnia, and acidosis) was associated with multiple indicators of brain damage. However, for some, the associations were seen with only 1 day of exposure; others were evident with 2 or more days’ exposure. Findings suggest that individual blood gas derangements do not increase brain damage risk. Rather, the multiple derangements associated with indicators of brain damage might be indicators of immaturity/vulnerability and illness severity. PMID:20807736

  19. Abuse of amphetamines and structural abnormalities in the brain.

    PubMed

    Berman, Steven; O'Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D

    2008-10-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  20. Abuse of Amphetamines and Structural Abnormalities in Brain

    PubMed Central

    Berman, Steven; O’Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D.

    2009-01-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse, and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques that include manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common, and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre-existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  1. Electrocardiographic abnormalities and cardiac arrhythmias in structural brain lesions.

    PubMed

    Katsanos, Aristeidis H; Korantzopoulos, Panagiotis; Tsivgoulis, Georgios; Kyritsis, Athanassios P; Kosmidou, Maria; Giannopoulos, Sotirios

    2013-07-31

    Cardiac arrhythmias and electrocardiographic abnormalities are frequently observed after acute cerebrovascular events. The precise mechanism that leads to the development of these arrhythmias is still uncertain, though increasing evidence suggests that it is mainly due to autonomic nervous system dysregulation. In massive brain lesions sympathetic predominance and parasympathetic withdrawal during the first 72 h are associated with the occurrence of severe secondary complications in the first week. Right insular cortex lesions are also related with sympathetic overactivation and with a higher incidence of electrocardiographic abnormalities, mostly QT prolongation, in patients with ischemic stroke. Additionally, female sex and hypokalemia are independent risk factors for severe prolongation of the QT interval which subsequently results in malignant arrhythmias and poor outcome. The prognostic value of repolarization changes commonly seen after aneurysmal subarachnoid hemorrhage, such as ST segment, T wave, and U wave abnormalities, still remains controversial. In patients with traumatic brain injury both intracranial hypertension and cerebral hypoperfusion correlate with low heart rate variability and increased mortality. Given that there are no firm guidelines for the prevention or treatment of the arrhythmias that appear after cerebral incidents this review aims to highlight important issues on this topic. Selected patients with the aforementioned risk factors could benefit from electrocardiographic monitoring, reassessment of the medications that prolong QTc interval, and administration of antiadrenergic agents. Further research is required in order to validate these assumptions and to establish specific therapeutic strategies. PMID:22809542

  2. Abnormal antioxidant defence in some tissues of congenitally obese mice.

    PubMed Central

    Capel, I D; Dorrell, H M

    1984-01-01

    The concentration of lipoperoxides (estimated as thiobarbituric acid-reactive material) and some components of the antioxidant defence system have been compared in various tissues of lean and congenitally obese mice. NADPH-stimulated lipoperoxide generation in vitro was significantly higher in microsomes (microsomal fractions) prepared from obese hepatic tissue than lean. Plasma, liver and brain lipoperoxide concentration was significantly higher in obese mice. In blood derived from obese mice the concentration of non-enzymic antioxidants including caeruloplasmin and vitamin A was higher, but hepatic retinol concentration was lower in these animals. In all the tissues assayed the glutathione peroxidase activity against H2O2 was less than its activity against cumene hydroperoxide. Assayed with either substrate, glutathione peroxidase activity was significantly higher in the brain and blood of obese mice than their lean counterparts. Conversely, liver glutathione peroxidase was decreased in obese animals, representing 43% of the activity of the lean-mouse liver enzyme against H2O2 and 81% of the cumene hydroperoxide-reducing activity. The liver of obese mice had significantly less, and the kidneys more, oxidized glutathione than the corresponding tissues of lean mice. Further investigations on hepatic tissue indicated that glutathione reductase activity was lower in the obese animals, but there was no significant difference between glucose-6-phosphate dehydrogenase activity in obese and lean mice. PMID:6721863

  3. Gyrification brain abnormalities as predictors of outcome in anorexia nervosa.

    PubMed

    Favaro, Angela; Tenconi, Elena; Degortes, Daniela; Manara, Renzo; Santonastaso, Paolo

    2015-12-01

    Gyrification brain abnormalities are considered a marker of early deviations from normal developmental trajectories and a putative predictor of poor outcome in psychiatric disorders. The aim of this study was to explore cortical folding morphology in patients with anorexia nervosa (AN). A MRI brain study was conducted on 38 patients with AN, 20 fully recovered patients, and 38 healthy women. Local gyrification was measured with procedures implemented in FreeSurfer. Vertex-wise comparisons were carried out to compare: (1) AN patients and healthy women; (2) patients with a full remission at a 3-year longitudinal follow-up assessment and patients who did not recover. AN patients exhibited significantly lower gyrification when compared with healthy controls. Patients with a poor 3-year outcome had significantly lower baseline gyrification when compared to both healthy women and patients with full recovery at follow-up, even after controlling for the effects of duration of illness and gray matter volume. No significant correlation has been found between gyrification, body mass index, amount of weight loss, onset age, and duration of illness. Brain gyrification significantly predicted outcome at follow-up even after controlling for the effects of duration of illness and other clinical prognostic factors. Although the role of starvation in determining our findings cannot be excluded, our study showed that brain gyrification might be a predictor of outcome in AN. Further studies are needed to understand if brain gyrification abnormalities are indices of early neurodevelopmental alterations, the consequence of starvation, or the interaction between both factors. PMID:26374960

  4. Organization of brain tissue - Is the brain a noisy processor.

    NASA Technical Reports Server (NTRS)

    Adey, W. R.

    1972-01-01

    This paper presents some thoughts on functional organization in cerebral tissue. 'Spontaneous' wave and unit firing are considered as essential phenomena in the handling of information. Various models are discussed which have been suggested to describe the pseudorandom behavior of brain cells, leading to a view of the brain as an information processor and its role in learning, memory, remembering and forgetting.

  5. Mature brain tissue in the sacrococcygeal region.

    PubMed

    Shrestha, Binod Bade; Ghimire, Pradeep; Ghartimagar, Dilasma; Jwarchan, Bishnu; Lalchan, Subita; Karmacharya, Mikesh

    2016-01-01

    Complete mature brain tissue in sacrococcygeal region is a rare congenital anomaly in a newborn, which usually is misdiagnosed for sacrococcygeal teratoma. Glial tumor-like ependymoma is also common in sacrococcygeal area but mostly appears later in life. We present a case of complete heterotopic brain tissue in the sacrococcygeal region. The patient underwent total excision of mass with coccygectomy. To our knowledge it is the second case being reported. PMID:27194682

  6. Mature brain tissue in the sacrococcygeal region

    PubMed Central

    Shrestha, Binod Bade; Ghimire, Pradeep; Ghartimagar, Dilasma; Jwarchan, Bishnu; Lalchan, Subita; Karmacharya, Mikesh

    2016-01-01

    Complete mature brain tissue in sacrococcygeal region is a rare congenital anomaly in a newborn, which usually is misdiagnosed for sacrococcygeal teratoma. Glial tumor-like ependymoma is also common in sacrococcygeal area but mostly appears later in life. We present a case of complete heterotopic brain tissue in the sacrococcygeal region. The patient underwent total excision of mass with coccygectomy. To our knowledge it is the second case being reported. PMID:27194682

  7. Abnormal trigeminal nerve microstructure and brain white matter in idiopathic trigeminal neuralgia.

    PubMed

    DeSouza, Danielle D; Hodaie, Mojgan; Davis, Karen D

    2014-01-01

    Idiopathic trigeminal neuralgia (TN) is classically associated with neurovascular compression (NVC) of the trigeminal nerve at the root entry zone (REZ), but NVC-induced structural alterations are not always apparent on conventional imaging. Previous studies report lower fractional anisotropy (FA) in the affected trigeminal nerves of TN patients using diffusion tensor imaging (DTI). However, it is not known if TN patients have trigeminal nerve abnormalities of mean, radial, or axial diffusivity (MD, RD, AD - metrics linked to neuroinflammation and edema) or brain white matter (WM) abnormalities. DTI scans in 18 right-sided TN patients and 18 healthy controls were retrospectively analyzed to extract FA, RD, AD, and MD from the trigeminal nerve REZ, and Tract-Based Spatial Statistics (TBSS) was used to assess brain WM. In patients, the affected trigeminal nerve had lower FA, and higher RD, AD, and MD was found bilaterally compared to controls. Group TBSS (P<0.05, corrected) showed patients had lower FA and increased RD, MD, and AD in brain WM connecting areas involved in the sensory and cognitive-affective dimensions of pain, attention, and motor functions, including the corpus callosum, cingulum, posterior corona radiata, and superior longitudinal fasciculus. These data indicate that TN patients have abnormal tissue microstructure in their affected trigeminal nerves, and as a possible consequence, WM microstructural alterations in the brain. These findings suggest that trigeminal nerve structural abnormalities occur in TN, even if not apparent on gross imaging. Furthermore, MD and RD findings suggest that neuroinflammation and edema may contribute to TN pathophysiology. PMID:23999058

  8. Neuroendocrine abnormalities in patients with traumatic brain injury

    NASA Technical Reports Server (NTRS)

    Yuan, X. Q.; Wade, C. E.

    1991-01-01

    This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture

  9. In vivo detection of epileptic brain tissue using static fluorescence and diffuse reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Yadav, Nitin; Bhatia, Sanjiv; Ragheb, John; Mehta, Rupal; Jayakar, Prasanna; Yong, William; Lin, Wei-Chiang

    2013-02-01

    Diffuse reflectance and fluorescence spectroscopy are used to detect histopathological abnormalities of an epileptic brain in a human subject study. Static diffuse reflectance and fluorescence spectra are acquired from normal and epileptic brain areas, defined by electrocorticography (ECoG), from pediatric patients undergoing epilepsy surgery. Biopsy specimens are taken from the investigated sites within an abnormal brain. Spectral analysis reveals significant differences in diffuse reflectance spectra and the ratio of fluorescence and diffuse reflectance spectra from normal and epileptic brain areas defined by ECoG and histology. Using these spectral differences, tissue classification models with accuracy above 80% are developed based on linear discriminant analysis. The differences between the diffuse reflectance spectra from the normal and epileptic brain areas observed in this study are attributed to alterations in the static hemodynamic characteristics of an epileptic brain, suggesting a unique association between the histopathological and the hemodynamic abnormalities in an epileptic brain.

  10. Anatomical and functional brain abnormalities in unmedicated major depressive disorder

    PubMed Central

    Yang, Xiao; Ma, Xiaojuan; Li, Mingli; Liu, Ye; Zhang, Jian; Huang, Bin; Zhao, Liansheng; Deng, Wei; Li, Tao; Ma, Xiaohong

    2015-01-01

    Background Using magnetic resonance imaging (MRI) and resting-state functional magnetic resonance imaging (rsfMRI) to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD). Patients and methods Fifty patients with MDD and 50 matched healthy control participants free of psychotropic medication underwent high-resolution structural and rsfMRI scanning. Optimized diffeomorphic anatomical registration through exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used to find potential differences in gray-matter volume (GMV) and regional homogeneity (ReHo) between the two groups. A Pearson correlation model was used to analyze associations of morphometric and functional changes with clinical symptoms. Results Compared to healthy controls, patients with MDD showed significant GMV increase in the left posterior cingulate gyrus and GMV decrease in the left lingual gyrus (P<0.001, uncorrected). In ReHo analysis, values were significantly increased in the left precuneus and decreased in the left putamen (P<0.001, uncorrected) in patients with MDD compared to healthy controls. There was no overlap between anatomical and functional changes. Linear correlation suggested no significant correlation between mean GMV values within regions with anatomical abnormality and ReHo values in regions with functional abnormality in the patient group. These changes were not significantly correlated with symptom severity. Conclusion Our study suggests a dissociation pattern of brain regions with anatomical and functional alterations in unmedicated patients with MDD, especially with regard to GMV and ReHo. PMID:26425096

  11. Brain abnormalities in human obesity: a voxel-based morphometric study.

    PubMed

    Pannacciulli, Nicola; Del Parigi, Angelo; Chen, Kewei; Le, Duc Son N T; Reiman, Eric M; Tataranni, Pietro A

    2006-07-15

    Obesity is accompanied by damage to several tissues. Overweight is a risk factor for Alzheimer's disease and other neurodegenerative disorders. Whether structural abnormalities associated with excess body fat may also occur in the brain is unknown. We sought to determine to what extent excess body fat is associated with regional alterations in brain structure using voxel-based morphometry (VBM), a whole-brain unbiased technique based upon high-definition 3D magnetic resonance imaging (MRI) scans normalized into a common standard space and allowing for an objective assessment of neuroanatomical differences throughout the brain. We studied 24 obese (11 male, 13 female; age: 32 +/- 8 years; body mass index [BMI]: 39.4 +/- 4.7 kg/m2) and 36 lean (25 male, 11 female; mean age: 33 +/- 9 years; BMI: 22.7 +/- 2.2 kg/m2) non-diabetic Caucasians. In comparison with the group of lean subjects, the group of obese individuals had significantly lower gray matter density in the post-central gyrus, frontal operculum, putamen, and middle frontal gyrus (P < 0.01 after adjustment for sex, age, handedness, global tissue density, and multiple comparisons). BMI was negatively associated with GM density of the left post-central gyrus in obese but not lean subjects. This study identified structural brain differences in human obesity in several brain areas previously involved in the regulation of taste, reward, and behavioral control. These alterations may either precede obesity, representing a neural marker of increased propensity to gaining weight, or occur as a consequence of obesity, indicating that also the brain is affected by increased adiposity. PMID:16545583

  12. Novel instrumentation of multispectral imaging technology for detecting tissue abnormity

    NASA Astrophysics Data System (ADS)

    Yi, Dingrong; Kong, Linghua

    2012-10-01

    Multispectral imaging is becoming a powerful tool in a wide range of biological and clinical studies by adding spectral, spatial and temporal dimensions to visualize tissue abnormity and the underlying biological processes. A conventional spectral imaging system includes two physically separated major components: a band-passing selection device (such as liquid crystal tunable filter and diffraction grating) and a scientific-grade monochromatic camera, and is expensive and bulky. Recently micro-arrayed narrow-band optical mosaic filter was invented and successfully fabricated to reduce the size and cost of multispectral imaging devices in order to meet the clinical requirement for medical diagnostic imaging applications. However the challenging issue of how to integrate and place the micro filter mosaic chip to the targeting focal plane, i.e., the imaging sensor, of an off-shelf CMOS/CCD camera is not reported anywhere. This paper presents the methods and results of integrating such a miniaturized filter with off-shelf CMOS imaging sensors to produce handheld real-time multispectral imaging devices for the application of early stage pressure ulcer (ESPU) detection. Unlike conventional multispectral imaging devices which are bulky and expensive, the resulting handheld real-time multispectral ESPU detector can produce multiple images at different center wavelengths with a single shot, therefore eliminates the image registration procedure required by traditional multispectral imaging technologies.

  13. The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

    PubMed

    Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

    2005-09-01

    The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group. PMID:16225232

  14. Mapping abnormal subcortical brain morphometry in an elderly HIV + cohort

    PubMed Central

    Wade, Benjamin S.C.; Valcour, Victor G.; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H.; Gutman, Boris A.; Thompson, Paul M.

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%. PMID:26640768

  15. Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation

    PubMed Central

    Beare, Richard J.; Chen, Jian; Kelly, Claire E.; Alexopoulos, Dimitrios; Smyser, Christopher D.; Rogers, Cynthia E.; Loh, Wai Y.; Matthews, Lillian G.; Cheong, Jeanie L. Y.; Spittle, Alicia J.; Anderson, Peter J.; Doyle, Lex W.; Inder, Terrie E.; Seal, Marc L.; Thompson, Deanne K.

    2016-01-01

    matter for coronal images acquired at 30 weeks. This demonstrates that MANTiS' performance is competitive with existing techniques. For the WUNDeR dataset, mean Dice scores comparing MANTiS with manually edited segmentations demonstrated good agreement, where all scores were above 0.75, except for the hippocampus and amygdala. The results show that MANTiS is able to segment neonatal brain tissues well, even in images that have brain abnormalities common in preterm infants. MANTiS is available for download as an SPM toolbox from http://developmentalimagingmcri.github.io/mantis. PMID:27065840

  16. Diffusion MRI at 25: Exploring brain tissue structure and function

    PubMed Central

    Bihan, Denis Le; Johansen-Berg, Heidi

    2013-01-01

    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. PMID:22120012

  17. Brain white matter abnormality in a newborn infant with congenital adrenal hyperplasia.

    PubMed

    Kaga, Akimune; Saito-Hakoda, Akiko; Uematsu, Mitsugu; Kamimura, Miki; Kanno, Junko; Kure, Shigeo; Fujiwara, Ikuma

    2013-10-01

    Several studies have described brain white matter abnormalities on magnetic resonance imaging (MRI) in children and adults with congenital adrenal hyperplasia (CAH), while the brain MRI findings of newborn infants with CAH have not been clarified. We report a newborn boy with CAH who presented brain white matter abnormality on MRI. He was diagnosed as having salt-wasting CAH with a high 17-OHP level at neonatal screening and was initially treated with hydrocortisone at 8 days of age. On day 11 after birth, he had a generalized tonic seizure. No evidence of serum electrolyte abnormalities was observed. Brain MRI revealed white matter abnormalities that consisted of bilateral small diffuse hyperintensities on T1-weighted images with slightly low intensity on T2-weighted images in the watershed area. Several factors associated with brain white matter abnormalities in adults with CAH, such as increasing age, hypertension, diabetes and corticosteroid replacement, were not applicable. Although the cause of the phenomenon in this case is unclear, brain white matter abnormality could be observed in newborn infants with CAH as well as in adult patients. PMID:24170965

  18. Investigating individual differences in brain abnormalities in autism.

    PubMed Central

    Salmond, C H; de Haan, M; Friston, K J; Gadian, D G; Vargha-Khadem, F

    2003-01-01

    Autism is a psychiatric syndrome characterized by impairments in three domains: social interaction, communication, and restricted and repetitive behaviours and interests. Recent findings implicate the amygdala in the neurobiology of autism. In this paper, we report the results of a series of novel experimental investigations focusing on the structure and function of the amygdala in a group of children with autism. The first section attempts to determine if abnormality of the amygdala can be identified in an individual using magnetic resonance imaging in vivo. Using single-case voxel-based morphometric analyses, abnormality in the amygdala was detected in half the children with autism. Abnormalities in other regions were also found. In the second section, emotional modulation of the startle response was investigated in the group of autistic children. Surprisingly, there were no significant differences between the patterns of emotional modulation of the startle response in the autistic group compared with the controls. PMID:12639337

  19. Infantile Autism and Computerized Tomography Brain-Scan Findings: Specific versus Nonspecific Abnormalities.

    ERIC Educational Resources Information Center

    Balottin, Umberto; And Others

    1989-01-01

    The study of computerized tomography brain-scan findings with 45 autistic and 19 control subjects concluded that autism is nonspecifically associated with brain-scan abnormalities, and that other nonorganic, as well as organic, factors should be taken into account. (Author/DB)

  20. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  1. Developmental vitamin D deficiency causes abnormal brain development.

    PubMed

    Eyles, D W; Feron, F; Cui, X; Kesby, J P; Harms, L H; Ko, P; McGrath, J J; Burne, T H J

    2009-12-01

    There is now clear evidence that vitamin D is involved in brain development. Our group is interested in environmental factors that shape brain development and how this may be relevant to neuropsychiatric diseases including schizophrenia. The origins of schizophrenia are considered developmental. We hypothesised that developmental vitamin D (DVD) deficiency may be the plausible neurobiological explanation for several important epidemiological correlates of schizophrenia namely: (1) the excess winter/spring birth rate, (2) increased incidence of the disease in 2nd generation Afro-Caribbean migrants and (3) increased urban birth rate. Moreover we have published two pieces of direct epidemiological support for this hypothesis in patients. In order to establish the "Biological Plausibility" of this hypothesis we have developed an animal model to study the effect of DVD deficiency on brain development. We do this by removing vitamin D from the diet of female rats prior to breeding. At birth we return all dams to a vitamin D containing diet. Using this procedure we impose a transient, gestational vitamin D deficiency, while maintaining normal calcium levels throughout. The brains of offspring from DVD-deficient dams are characterised by (1) a mild distortion in brain shape, (2) increased lateral ventricle volumes, (3) reduced differentiation and (4) diminished expression of neurotrophic factors. As adults, the alterations in ventricular volume persist and alterations in brain gene and protein expression emerge. Adult DVD-deficient rats also display behavioural sensitivity to agents that induce psychosis (the NMDA antagonist MK-801) and have impairments in attentional processing. In this review we summarise the literature addressing the function of vitamin D on neuronal and non-neuronal cells as well as in vivo results from DVD-deficient animals. Our conclusions from these data are that vitamin D is a plausible biological risk factor for neuropsychiatric disorders and that

  2. Abnormal deposits of chromium in the pathological human brain.

    PubMed Central

    Duckett, S

    1986-01-01

    Three patients presented with encephalopathies: an undiagnosed degenerative disease of the brain, a degenerative cerebral disease in a patient with a myeloma but without a myelomatous deposit in the CNS and a malignant astrocytoma. Perivascular pallidal deposits (vascular siderosis) containing chromium, phosphorus and calcium plus sometimes traces of other elements were present in the three cases. Such deposits were present in the pallidal parenchyma and around vessels in the cerebellum in one case. Calcium and phosphorus are always present in any CNS calcification but the presence of chromium has not been reported. Chromium and its compounds (ingested, injected or inhaled) are toxic to humans and animals in trace doses. Approximately 900 cases of chromium intoxication have been reported and usually have had dermatological or pulmonary lesions (including cancer) but there is no report of involvement of the CNS. Sublethal doses of chromium nitrate injected intraperitoneally in rats and rabbits results in the presence of chromium in the brain. A thorough investigation was made to find the source of the chromium in these patients. Chromium was found to be present in trace amounts in the radiological contrast agents administered to these patients and in the KCl replacement solution and in mylanta, an antacid, given to one case. The evidence that chromium induced pathological changes in these three brains is circumstantial but shows that chromium can penetrate the human brain. This study indicates that vascular siderosis found in the brains of the majority of middle-aged and elderly humans is not simply an anecdotal pathological curiosity, but that it can serve as a route of entry for toxic products into the brain. Images PMID:3958742

  3. Conditional Tat protein brain expression in the GT-tg bigenic mouse induces cerebral fractional anisotropy abnormalities

    PubMed Central

    Carey, Amanda N.; Liu, Xiaoxu; Mintzopoulos, Dionyssios; Paris, Jason J.; McLaughlin, Jay P.; Kaufman, Marc J.

    2015-01-01

    Cerebral white matter changes including tissue water diffusion abnormalities detected with diffusion tensor magnetic resonance imaging (DTI) are commonly found in humans with Human Immunodeficiency Virus (HIV) infection, as well as in animal models of the disorder. The severities of some of these abnormalities have been reported to correlate with measures of disease progression or severity, or with the degree of cognitive dysfunction. Accordingly, DTI may be a useful translational biomarker. HIV-Tat protein appears to be an important factor in the viral pathogenesis of HIV-associated neurotoxicity. We previously reported cerebral gray matter density reductions in the GT-tg bigenic mouse treated with doxycycline (Dox) to conditionally induce Tat protein expression. Presently, we administered intraperitoneal (i.p.) Dox (100 mg/kg/day) for 7 days to GT-tg mice to determine whether induction of conditional Tat expression led to the development of cerebral DTI abnormalities. Perfused and fixed brains from eight GT-tg mice administered Dox and eight control mice administered saline i.p. were extracted and underwent DTI scans on a 9.4 Tesla scanner. A whole brain analysis detected fractional anisotropy (FA) reductions in several areas including insular and endopiriform regions, as well as within the dorsal striatum. These findings suggest that exposure to Tat protein is sufficient to induce FA abnormalities, and further support the use of the GT-tg mouse to model some effects of HIV. PMID:25619988

  4. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  5. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    ERIC Educational Resources Information Center

    Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

    2013-01-01

    Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

  6. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    SciTech Connect

    D'Aprile, P.; Carella, A.; Pagliarulo, R. ); Farchi, G. )

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  7. Abnormal brain structure in youth who commit homicide

    PubMed Central

    Cope, L.M.; Ermer, E.; Gaudet, L.M.; Steele, V.R.; Eckhardt, A.L.; Arbabshirani, M.R.; Caldwell, M.F.; Calhoun, V.D.; Kiehl, K.A.

    2014-01-01

    Background Violence that leads to homicide results in an extreme financial and emotional burden on society. Juveniles who commit homicide are often tried in adult court and typically spend the majority of their lives in prison. Despite the enormous costs associated with homicidal behavior, there have been no serious neuroscientific studies examining youth who commit homicide. Methods Here we use neuroimaging and voxel-based morphometry to examine brain gray matter in incarcerated male adolescents who committed homicide (n = 20) compared with incarcerated offenders who did not commit homicide (n = 135). Two additional control groups were used to understand further the nature of gray matter differences: incarcerated offenders who did not commit homicide matched on important demographic and psychometric variables (n = 20) and healthy participants from the community (n = 21). Results Compared with incarcerated adolescents who did not commit homicide (n = 135), incarcerated homicide offenders had reduced gray matter volumes in the medial and lateral temporal lobes, including the hippocampus and posterior insula. Feature selection and support vector machine learning classified offenders into the homicide and non-homicide groups with 81% overall accuracy. Conclusions Our results indicate that brain structural differences may help identify those at the highest risk for committing serious violent offenses. PMID:24936430

  8. scMRI Reveals Large-Scale Brain Network Abnormalities in Autism

    PubMed Central

    Zielinski, Brandon A.; Anderson, Jeffrey S.; Froehlich, Alyson L.; Prigge, Molly B. D.; Nielsen, Jared A.; Cooperrider, Jason R.; Cariello, Annahir N.; Fletcher, P. Thomas; Alexander, Andrew L.; Lange, Nicholas; Bigler, Erin D.; Lainhart, Janet E.

    2012-01-01

    Autism is a complex neurological condition characterized by childhood onset of dysfunction in multiple cognitive domains including socio-emotional function, speech and language, and processing of internally versus externally directed stimuli. Although gross brain anatomic differences in autism are well established, recent studies investigating regional differences in brain structure and function have yielded divergent and seemingly contradictory results. How regional abnormalities relate to the autistic phenotype remains unclear. We hypothesized that autism exhibits distinct perturbations in network-level brain architecture, and that cognitive dysfunction may be reflected by abnormal network structure. Network-level anatomic abnormalities in autism have not been previously described. We used structural covariance MRI to investigate network-level differences in gray matter structure within two large-scale networks strongly implicated in autism, the salience network and the default mode network, in autistic subjects and age-, gender-, and IQ-matched controls. We report specific perturbations in brain network architecture in the salience and default-mode networks consistent with clinical manifestations of autism. Extent and distribution of the salience network, involved in social-emotional regulation of environmental stimuli, is restricted in autism. In contrast, posterior elements of the default mode network have increased spatial distribution, suggesting a ‘posteriorization’ of this network. These findings are consistent with a network-based model of autism, and suggest a unifying interpretation of previous work. Moreover, we provide evidence of specific abnormalities in brain network architecture underlying autism that are quantifiable using standard clinical MRI. PMID:23185305

  9. MRI-based methods to detect placental and fetal brain abnormalities in utero.

    PubMed

    Girardi, Guillermina

    2016-04-01

    There are very few methods for screening women for pregnancy complications. Identification of pregnancies at risk would be of enormous clinical significance as would influence decisions made about pregnancy management and delivery. Adverse pregnancy outcomes such as obstetric antiphospholipid syndrome (APS) and preterm birth (PTB), characterized by placental insufficiency and abnormal fetal brain development, in mice and humans have been associated with activation of inflammatory pathways, in particular the complement cascade. Recently, antibodies against C3 activation products conjugated with contrast agent ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were used to detect non-invasively sites of inflammation within the placenta and the fetal brain in mouse models of APS and PTB. In utero, magnetic resonance imaging (MRI)-based detection of C3 deposition in the placenta in the APS model was associated with signs of placental insufficiency and intrauterine growth restriction. In both models, fetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration. Proton magnetic resonance spectroscopy ((1)H MRS), another non invasive method, is used to identify metabolic abnormalities to predict fetal brain abnormalities. This review describes the recent development of preclinical MRI-based methods for the detection of inflammatory markers of placental insufficiency and abnormal fetal brain development and metabolism to predict pregnancy outcomes. PMID:26187242

  10. Abnormal subcellular localization of GABAA receptor subunits in schizophrenia brain.

    PubMed

    Mueller, T M; Remedies, C E; Haroutunian, V; Meador-Woodruff, J H

    2015-01-01

    Inhibitory neurotransmission is primarily mediated by γ-aminobutyric acid (GABA) activating synaptic GABA type A receptors (GABA(A)R). In schizophrenia, presynaptic GABAergic signaling deficits are among the most replicated findings; however, postsynaptic GABAergic deficits are less well characterized. Our lab has previously demonstrated that although there is no difference in total protein expression of the α1-6, β1-3 or γ2 GABA(A)R subunits in the superior temporal gyrus (STG) in schizophrenia, the α1, β1 and β2 GABA(A)R subunits are abnormally N-glycosylated. N-glycosylation is a posttranslational modification that has important functional roles in protein folding, multimer assembly and forward trafficking. To investigate the impact that altered N-glycosylation has on the assembly and trafficking of GABA(A)Rs in schizophrenia, this study used western blot analysis to measure the expression of α1, α2, β1, β2 and γ2 GABA(A)R subunits in subcellular fractions enriched for endoplasmic reticulum (ER) and synapses (SYN) from STG of schizophrenia (N = 16) and comparison (N = 14) subjects and found evidence of abnormal localization of the β1 and β2 GABA(A)R subunits and subunit isoforms in schizophrenia. The β2 subunit is expressed as three isoforms at 52 kDa (β2(52 kDa)), 50 kDa (β2(50 kDa)) and 48 kDa (β2(48 kDa)). In the ER, we found increased total β2 GABA(A)R subunit (β2(ALL)) expression driven by increased β2(50 kDa), a decreased ratio of β(248 kDa):β2(ALL) and an increased ratio of β2(50 kDa):β2(48 kDa). Decreased ratios of β1:β2(ALL) and β1:β2(50 kDa) in both the ER and SYN fractions and an increased ratio of β2(52 kDa):β(248 kDa) at the synapse were also identified in schizophrenia. Taken together, these findings provide evidence that alterations of N-glycosylation may contribute to GABAergic signaling deficits in schizophrenia by disrupting the assembly and trafficking of GABA(A)Rs. PMID:26241350

  11. Abnormal subcellular localization of GABAA receptor subunits in schizophrenia brain

    PubMed Central

    Mueller, T M; Remedies, C E; Haroutunian, V; Meador-Woodruff, J H

    2015-01-01

    Inhibitory neurotransmission is primarily mediated by γ-aminobutyric acid (GABA) activating synaptic GABA type A receptors (GABAAR). In schizophrenia, presynaptic GABAergic signaling deficits are among the most replicated findings; however, postsynaptic GABAergic deficits are less well characterized. Our lab has previously demonstrated that although there is no difference in total protein expression of the α1–6, β1–3 or γ2 GABAAR subunits in the superior temporal gyrus (STG) in schizophrenia, the α1, β1 and β2 GABAAR subunits are abnormally N-glycosylated. N-glycosylation is a posttranslational modification that has important functional roles in protein folding, multimer assembly and forward trafficking. To investigate the impact that altered N-glycosylation has on the assembly and trafficking of GABAARs in schizophrenia, this study used western blot analysis to measure the expression of α1, α2, β1, β2 and γ2 GABAAR subunits in subcellular fractions enriched for endoplasmic reticulum (ER) and synapses (SYN) from STG of schizophrenia (N=16) and comparison (N=14) subjects and found evidence of abnormal localization of the β1 and β2 GABAAR subunits and subunit isoforms in schizophrenia. The β2 subunit is expressed as three isoforms at 52 kDa (β252 kDa), 50 kDa (β250 kDa) and 48 kDa (β248 kDa). In the ER, we found increased total β2 GABAAR subunit (β2ALL) expression driven by increased β250 kDa, a decreased ratio of β248 kDa:β2ALL and an increased ratio of β250 kDa:β248 kDa. Decreased ratios of β1:β2ALL and β1:β250 kDa in both the ER and SYN fractions and an increased ratio of β252 kDa:β248 kDa at the synapse were also identified in schizophrenia. Taken together, these findings provide evidence that alterations of N-glycosylation may contribute to GABAergic signaling deficits in schizophrenia by disrupting the assembly and trafficking of GABAARs. PMID:26241350

  12. NMR imaging of cell phone radiation absorption in brain tissue

    PubMed Central

    Gultekin, David H.; Moeller, Lothar

    2013-01-01

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

  13. NMR imaging of cell phone radiation absorption in brain tissue.

    PubMed

    Gultekin, David H; Moeller, Lothar

    2013-01-01

    A method is described for measuring absorbed electromagnetic energy radiated from cell phone antennae into ex vivo brain tissue. NMR images the 3D thermal dynamics inside ex vivo bovine brain tissue and equivalent gel under exposure to power and irradiation time-varying radio frequency (RF) fields. The absorbed RF energy in brain tissue converts into Joule heat and affects the nuclear magnetic shielding and the Larmor precession. The resultant temperature increase is measured by the resonance frequency shift of hydrogen protons in brain tissue. This proposed application of NMR thermometry offers sufficient spatial and temporal resolution to characterize the hot spots from absorbed cell phone radiation in aqueous media and biological tissues. Specific absorption rate measurements averaged over 1 mg and 10 s in the brain tissue cover the total absorption volume. Reference measurements with fiber optic temperature sensors confirm the accuracy of the NMR thermometry. PMID:23248293

  14. Maternal immune activation and abnormal brain development across CNS disorders.

    PubMed

    Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P

    2014-11-01

    Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies. PMID:25311587

  15. Absence of Glial α-Dystrobrevin Causes Abnormalities of the Blood-Brain Barrier and Progressive Brain Edema*

    PubMed Central

    Lien, Chun Fu; Mohanta, Sarajo Kumar; Frontczak-Baniewicz, Malgorzata; Swinny, Jerome D.; Zablocka, Barbara; Górecki, Dariusz C.

    2012-01-01

    The blood-brain barrier (BBB) plays a key role in maintaining brain functionality. Although mammalian BBB is formed by endothelial cells, its function requires interactions between endotheliocytes and glia. To understand the molecular mechanisms involved in these interactions is currently a major challenge. We show here that α-dystrobrevin (α-DB), a protein contributing to dystrophin-associated protein scaffolds in astrocytic endfeet, is essential for the formation and functioning of BBB. The absence of α-DB in null brains resulted in abnormal brain capillary permeability, progressively escalating brain edema, and damage of the neurovascular unit. Analyses in situ and in two-dimensional and three-dimensional in vitro models of BBB containing α-DB-null astrocytes demonstrated these abnormalities to be associated with loss of aquaporin-4 water and Kir4.1 potassium channels from glial endfeet, formation of intracellular vacuoles in α-DB-null astrocytes, and defects of the astrocyte-endothelial interactions. These caused deregulation of tight junction proteins in the endothelia. Importantly, α-DB but not dystrophins showed continuous expression throughout development in BBB models. Thus, α-DB emerges as a central organizer of dystrophin-associated protein in glial endfeet and a rare example of a glial protein with a role in maintaining BBB function. Its abnormalities might therefore lead to BBB dysfunction. PMID:23043099

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

    NASA Technical Reports Server (NTRS)

    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. The MEG topography and the source model of abnormal neural activities associated with brain lesions

    SciTech Connect

    Ueno, S.; Iramina, K.; Ozaki, H.; Harada, K.

    1986-09-01

    A source model is proposed to simulate spatial distributions of abnormal MEG and EEG activities generated by abnormal neural activities such as the delta activity associated with brain tumors. Brain tumor itself is electrically silent and the spherical shell around the tumor might generate abnormal neural activities. The sources of these neural activities are represented by combinations of multiple current dipoles. The head is assumed to be a spherical volume conductor. Electrical potentials and magnetic fields over the surface of the spheres are calculated. The computer simulation shows that the MEG topography and EEG topography vary variously with combinations of location and orientation of the dipoles. In a special case, however, that the dipoles orient in the same direction or orient radially, the spatial patterns of the MEGs and EEGs generated by numerous dipoles are analogous to those generated by single dipoles.

  18. Preliminary research on abnormal brain detection by wavelet-energy and quantum- behaved PSO.

    PubMed

    Zhang, Yudong; Ji, Genlin; Yang, Jiquan; Wang, Shuihua; Dong, Zhengchao; Phillips, Preetha; Sun, Ping

    2016-04-29

    It is important to detect abnormal brains accurately and early. The wavelet-energy (WE) was a successful feature descriptor that achieved excellent performance in various applications; hence, we proposed a WE based new approach for automated abnormal detection, and reported its preliminary results in this study. The kernel support vector machine (KSVM) was used as the classifier, and quantum-behaved particle swarm optimization (QPSO) was introduced to optimize the weights of the SVM. The results based on a 5 × 5-fold cross validation showed the performance of the proposed WE + QPSO-KSVM was superior to ``DWT + PCA + BP-NN'', ``DWT + PCA + RBF-NN'', ``DWT + PCA + PSO-KSVM'', ``WE + BPNN'', ``WE +$ KSVM'', and ``DWT $+$ PCA $+$ GA-KSVM'' w.r.t. sensitivity, specificity, and accuracy. The work provides a novel means to detect abnormal brains with excellent performance. PMID:27163327

  19. Abnormal Corticospinal Excitability in Traumatic Diffuse Axonal Brain Injury

    PubMed Central

    Bernabeu, Montse; Demirtas-Tatlidede, Asli; Opisso, Eloy; Lopez, Raquel; Tormos, Jose Mª

    2009-01-01

    Abstract This study aimed to investigate the cortical motor excitability characteristics in diffuse axonal injury (DAI) due to severe traumatic brain injury (TBI). A variety of excitatory and inhibitory transcranial magnetic stimulation (TMS) paradigms were applied to primary motor cortices of 17 patients and 11 healthy controls. The parameters of testing included resting motor threshold (MT), motor evoked potential (MEP) area under the curve, input-output curves, MEP variability, and silent period (SP) duration. The patient group overall revealed a higher MT, smaller MEP areas, and narrower recruitment curves compared to normal controls (p < 0.05). The alterations in excitability were more pronounced with an increase in DAI severity (p < 0.005) and the presence of motor impairment (p < 0.05), while co-existence of focal lesions did not affect the degree of MEP changes. MEP variability was significantly lower in the group with motor impairment only (p < 0.05). The intracortical inhibition, as revealed by SP duration, did not exhibit any significant differences in any of the patient groups. In conclusion, our findings expand the concept that impairment of the excitatory and inhibitory phenomena in the motor cortex does not proceed in parallel and demonstrate distinct patterns of aberrations in TBI. Furthermore, these data suggest that alterations in the corticospinal excitatory mechanisms are determined predominantly by the severity of DAI, and show a significant relationship with clinical motor dysfunction following severe trauma diffusely affecting the motor cortical connections. In severe TBI, motor and functional recovery might be linked to restitution of normal corticospinal mechanisms, indexed by normalization of the cortical excitability parameters. PMID:19604100

  20. Abnormal Parietal Brain Function in ADHD: Replication and Extension of Previous EEG Beta Asymmetry Findings

    PubMed Central

    Hale, T. Sigi; Kane, Andrea M.; Tung, Kelly L.; Kaminsky, Olivia; McGough, James J.; Hanada, Grant; Loo, Sandra K.

    2014-01-01

    Background: Abundant work indicates ADHD abnormal posterior brain structure and function, including abnormal structural and functional asymmetries and reduced corpus callosum size. However, this literature has attracted considerably less research interest than fronto-striatal findings. Objective: To help address this imbalance, the current study replicates and extends our previous work showing abnormal parietal brain function in ADHD adults during the Conner’s Continuous Performance Test (CPT). Method: Our previous study found that ADHD adults had increased rightward EEG beta (16–21 Hz) asymmetry in inferior parietal brain regions during the CPT (p = 0.00001), and that this metric exhibited a lack of normal correlation (i.e., observed in controls) with beta asymmetry at temporal–parietal regions. We re-tested these effects in a new ADHD sample and with both new and old samples combined. We additionally examined: (a) EEG asymmetry in multiple frequency bands, (b) unilateral effects for all asymmetry findings, and (c) the association between EEG asymmetry and a battery of cognitive tests. Results: We replicated our original findings by demonstrating abnormal rightward inferior parietal beta asymmetry in adults with ADHD during the CPT, and again this metric exhibited abnormal reduced correlation to temporal–parietal beta asymmetry. Novel analyses also demonstrated a broader pattern of rightward beta and theta asymmetry across inferior, superior, and temporal–parietal brain regions, and showed that rightward parietal asymmetry in ADHD was atypically associated with multiple cognitive tests. Conclusion: Abnormal increased rightward parietal EEG beta asymmetry is an important feature of ADHD. We speculate that this phenotype may occur with any form of impaired capacity for top-down task-directed control over sensory encoding functions, and that it may reflect associated increase of attentional shifting and compensatory sustained/selective attention. PMID

  1. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury.

    PubMed

    Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J; Diwakar, Mithun; Risbrough, Victoria B; Ji, Zhengwei; Huang, Charles W; Chang, Douglas G; Harrington, Deborah L; Muzzatti, Laura; Canive, Jose M; Christopher Edgar, J; Chen, Yu-Han; Lee, Roland R

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1-4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1-4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI. PMID:25009772

  2. Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

    PubMed Central

    Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G.; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A.; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J.; Diwakar, Mithun; Risbrough, Victoria B.; Ji, Zhengwei; Huang, Charles W.; Chang, Douglas G.; Harrington, Deborah L.; Muzzatti, Laura; Canive, Jose M.; Christopher Edgar, J.; Chen, Yu-Han; Lee, Roland R.

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI. PMID:25009772

  3. Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

    SciTech Connect

    Fujibayashi, Y.; Yamamoto, S.; Waki, A. |

    1996-05-01

    DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies. In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.

  4. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  5. Thallium-technetium parathyroid scan. A useful noninvasive technique for localization of abnormal parathyroid tissue

    SciTech Connect

    Manni, A.; Basarab, R.M.; Plourde, P.V.; Koivunen, D.; Harrison, T.S.; Santen, R.J.

    1986-06-01

    We studied the usefulness of the thallium-technetium scan in 60 patients with suspected parathyroid disorders. The scan correctly localized abnormal parathyroid tissue in 82% of patients with surgically proved primary hyperparathyroidism due to a single adenoma and in 60% of patients operated on for primary hyperplasia. The scan was particularly useful in patients who had undergone previous neck explorations, since it successfully identified residual adenomatous or hyperplastic tissue in six of seven patients. False-positive images were consistently produced in all patients with coexisting thyroid disease. We conclude that the thallium-technetium scan is useful for localizing abnormal parathyroid tissue. We recommend its routine use in patients with persistent or recurrent hypercalcemia following neck exploration for primary hyperparathyroidism who have no evidence of thyroid disorders.

  6. Measurement of steroid concentrations in brain tissue: methodological considerations.

    PubMed

    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

  7. Magnetic iron compounds in the human brain: a comparison of tumour and hippocampal tissue

    PubMed Central

    Brem, Franziska; Hirt, Ann M; Winklhofer, Michael; Frei, Karl; Yonekawa, Yasuhiro; Wieser, Heinz-Gregor; Dobson, Jon

    2006-01-01

    Iron is a central element in the metabolism of normal and malignant cells. Abnormalities in iron and ferritin expression have been observed in many types of cancer. Interest in characterizing iron compounds in the human brain has increased due to advances in determining a relationship between excess iron accumulation and neurological and neurodegenerative diseases. In this work, four different magnetic methods have been employed to characterize the iron phases and magnetic properties of brain tumour (meningiomas) tissues and non-tumour hippocampal tissues. Four main magnetic components can be distinguished: the diamagnetic matrix, nearly paramagnetic blood, antiferromagnetic ferrihydrite cores of ferritin and ferrimagnetic magnetite and/or maghemite. For the first time, open hysteresis loops have been observed on human brain tissue at room temperature. The hysteresis properties indicate the presence of magnetite and/or maghemite particles that exhibit stable single-domain (SD) behaviour at room temperature. A significantly higher concentration of magnetically ordered magnetite and/or maghemite and a higher estimated concentration of heme iron was found in the meningioma samples. First-order reversal curve diagrams on meningioma tissue further show that the stable SD particles are magnetostatically interacting, implying high-local concentrations (clustering) of these particles in brain tumours. These findings suggest that brain tumour tissue contains an elevated amount of remanent iron oxide phases. PMID:17015303

  8. Backscatter and attenuation properties of mammalian brain tissues

    NASA Astrophysics Data System (ADS)

    Wijekularatne, Pushpani Vihara

    Traumatic Brain Injury (TBI) is a common category of brain injuries, which contributes to a substantial number of deaths and permanent disability all over the world. Ultrasound technology plays a major role in tissue characterization due to its low cost and portability that could be used to bridge a wide gap in the TBI diagnostic process. This research addresses the ultrasonic properties of mammalian brain tissues focusing on backscatter and attenuation. Orientation dependence and spatial averaging of data were analyzed using the same method resulting from insertion of tissue sample between a transducer and a reference reflector. Apparent backscatter transfer function (ABTF) at 1 to 10 MHz, attenuation coefficient and backscatter coefficient (BSC) at 1 to 5 MHz frequency ranges were measured on ovine brain tissue samples. The resulting ABTF was a monotonically decreasing function of frequency and the attenuation coefficient and BSC generally were increasing functions of frequency, results consistent with other soft tissues such as liver, blood and heart.

  9. Cranial index of children with normal and abnormal brain development in Sokoto, Nigeria: A comparative study

    PubMed Central

    Musa, Muhammad Awwal; Zagga, Abdullahi Daudu; Danfulani, Mohammed; Tadros, Aziz Abdo; Ahmed, Hamid

    2014-01-01

    Background: Abnormal brain development due to neurodevelopmental disorders in children has always been an important concern, but yet has to be considered as a significant public health problem, especially in the low- and middle-income countries including Nigeria. Aims: The aim of this study is to determine whether abnormal brain development in the form of neurodevelopmental disorders causes any deviation in the cranial index of affected children. Materials and Methods: This is a comparative study on the head length, head width, and cranial index of 112 children (72 males and 40 females) diagnosed with at least one abnormal problem in brain development, in the form of a neurodevelopmental disorder (NDD), in comparison with that of 218 normal growing children without any form of NDD (121 males and 97 females), aged 0-18 years old seen at the Usmanu Danfodiyo University Teaching Hospital, Sokoto, over a period of six months, June to December, 2012. The head length and head width of the children was measured using standard anatomical landmarks and cranial index calculated. The data obtained was entered into the Microsoft excel worksheet and analyzed using SPSS version 17. Results: The mean Cephalic Index for normal growing children with normal brain development was 79.82 ± 3.35 and that of the children with abnormal brain development was 77.78 ± 2.95 and the difference between the two groups was not statistically significant (P > 0.05). Conclusion: It can be deduced from this present study that the cranial index does not change in children with neurodevelopmental disorders. PMID:24966551

  10. Red-Backed Vole Brain Promotes Highly Efficient In Vitro Amplification of Abnormal Prion Protein from Macaque and Human Brains Infected with Variant Creutzfeldt-Jakob Disease Agent

    PubMed Central

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in vCJD-infected human

  11. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    USGS Publications Warehouse

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  12. A mechanical model predicts morphological abnormalities in the developing human brain

    PubMed Central

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-01-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism. PMID:25008163

  13. A mechanical model predicts morphological abnormalities in the developing human brain

    NASA Astrophysics Data System (ADS)

    Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

    2014-07-01

    The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

  14. Limbic Metabolic Abnormalities in Remote Traumatic Brain Injury and Correlation With Psychiatric Morbidity and Social Functioning

    PubMed Central

    Capizzano, Arístides A.; Jorge, Ricardo E.; Robinson, Robert G.

    2013-01-01

    The aim of this study was to investigate limbic metabolic abnormalities in remote traumatic brain injury (TBI) and their psychiatric correlates. Twenty patients and 13 age-matched comparison subjects received complete psychiatric evaluation and brain MRI and MR spectroscopy at 3 Tesla. Patients had reduced NAA to creatine ratio in the left hippocampus relative to comparison subjects (mean=1.3 [SD=0.21] compared with mean=1.55 [SD=0.21]; F=10.73, df=1, 30, p=0.003), which correlated with the Social Functioning Examination scores (rs=−0.502, p=0.034). Furthermore, patients with mood disorders had reduced NAA to creatine ratio in the left cingulate relative to patients without mood disorders (1.47 compared with 1.68; F=3.393, df=3, 19, p=0.044). Remote TBI displays limbic metabolic abnormalities, which correlate to social outcome and psychiatric status. PMID:21037120

  15. An abnormal lymphatic phenotype is associated with subcutaneous adipose tissue deposits in Dercum’s disease

    PubMed Central

    Rasmussen, John C.; Herbst, Karen L.; Aldrich, Melissa B.; Darne, Chinmay D.; Tan, I-Chih; Zhu, Banghe; Guilliod, Renie; Fife, Caroline A.; Maus, Erik A.; Sevick-Muraca, Eva M.

    2014-01-01

    Objective Investigational, near-infrared fluorescence (NIRF) lymphatic imaging was used to assess lymphatic architecture and contractile function in participants diagnosed with Dercum’s disease, a rare, poorly understood disorder characterized by painful lipomas in subcutaneous adipose tissues. Design and Methods After informed consent and as part of an FDA-approved feasibility study to evaluate lymphatics in diseases in which their contribution has been implicated, three women diagnosed with Dercum’s disease and four control subjects were imaged. Each participant received multiple intradermal and subcutaneous injections of indocyanine green (ICG, total dose ≤400µg) in arms, legs, and/or trunk. Immediately after injection, ICG was taken up by the lymphatics and NIRF imaging was conducted. Results The lymphatics in the participants with Dercum’s disease were intact and dilated, yet sluggishly propelled lymph when compared to control lymphatics. Palpation of regions containing fluorescent lymphatic pathways revealed tender, fibrotic, tubular structures within the subcutaneous adipose tissue that were associated with painful nodules, and, in some cases, masses of fluorescent tissue indicating that some lipomas may represent tertiary lymphoid tissues. Conclusions These data support the hypothesis that Dercum’s disease may be a lymphovascular disorder and suggest a possible association between abnormal adipose tissue deposition and abnormal lymphatic structure and function. PMID:25044620

  16. Persistent endothelial abnormalities and blood-brain barrier leak in primary and secondary progressive multiple sclerosis.

    PubMed

    Leech, S; Kirk, J; Plumb, J; McQuaid, S

    2007-02-01

    Epithelial and endothelial tight junctions are pathologically altered in infectious, inflammatory, neoplastic and other diseases. Previously, we described such abnormalities, associated with serum protein leak, in tight junctions of the blood-brain barrier endothelium, in lesional and normal-appearing white matter (NAWM) in secondary progressive (SP) and acute multiple sclerosis (MS). This work is extended here to lesions and NAWM in primary progressive multiple sclerosis (PPMS) and to cortical grey matter in PPMS and SPMS. Immunocytochemistry and semiquantitative confocal microscopy for the tight junction protein zonula occludens 1 (ZO-1) was performed on snap-frozen sections from PPMS (n = 6) and controls (n = 5). Data on 2103 blood vessels were acquired from active lesions (n = 10), inactive lesions (n = 15), NAWM (n = 42) and controls (n = 20). Data on 1218 vessels were acquired from normal-appearing grey matter (PPMS, 5; SPMS, 6; controls, 5). In PPMS abnormal ZO-1 expression in active white matter lesions and NAWM, was found in 42% and 13% of blood vessels, respectively, comparable to previous data from acute and SPMS. In chronic white matter plaques, however, abnormalities were considerably more frequent (37%) in PPMS than in SPMS. Abnormality was also more frequent in normal-appearing grey matter in SPMS (23%) than in PPMS (10%). In summary, abnormal tight junctions in both SPMS and PPMS are most frequent in active white matter lesions but persist in inactive lesions, particularly in PPMS. Abnormal tight junctions are also common in normal-appearing grey matter in SPMS. Persistent endothelial abnormality with leak (PEAL) is therefore widespread but variably expressed in MS and may contribute to disease progression. PMID:17239011

  17. Simulation study of diffuse photon density waves traveling through normal and abnormal breast tissue

    NASA Astrophysics Data System (ADS)

    Deng, Xiaoyuan; Xing, Da

    1999-09-01

    Diffuse Photon Density Waves (DPDW) is new concept and principle, which takes advantage of the difference of absorption and scattering coefficients of different tissues to study the law of photon density fluctuation during a modulated light traveling through the tissues, thus to explore the structure and function of tissues. With the combination of image reconstruction technology, we can directly `visualize' the tissues. As a non- invasive exam, it has highly extensive applied prospect in medical field and brain cognition study. In this paper, the behavior of DPDW traveling through simulated breast tissue is tentatively examined. Under various conditions, we observed the characteristics of DPDW. We observed the reasonability of the distribution of sources and detectors, the factors that influence the distortion of DPDW. Simulation results could be used as a good theoretical guideline for experiments.

  18. The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia.

    PubMed

    Mansur, Rodrigo Barbachan; Brietzke, Elisa

    2012-09-01

    Metabolic abnormalities are frequent in patients with schizophrenia and bipolar disorder (BD), leading to a high prevalence of diabetes and metabolic syndrome in this population. Moreover, mortality rates among patients are higher than in the general population, especially due to cardiovascular diseases. Several neurobiological systems involved in energy metabolism have been shown to be altered in both illnesses; however, the cause of metabolic abnormalities and how they relate to schizophrenia and BD pathophysiology are still largely unknown. The "selfish brain" theory is a recent paradigm postulating that, in order to maintain its own energy supply stable, the brain modulates energy metabolism in the periphery by regulation of both allocation and intake of nutrients. We hypothesize that the metabolic alterations observed in these disorders are a result of an inefficient regulation of the brain energy supply and its compensatory mechanisms. The selfish brain theory can also expand our understanding of stress adaptation and neuroprogression in schizophrenia and BD, and, overall, can have important clinical implications for both illnesses. PMID:25923003

  19. Thalamic abnormalities are a cardinal feature of alcohol-related brain dysfunction.

    PubMed

    Pitel, Anne Lise; Segobin, Shailendra H; Ritz, Ludivine; Eustache, Francis; Beaunieux, Hélène

    2015-07-01

    Two brain networks are particularly affected by the harmful effect of chronic and excessive alcohol consumption: the circuit of Papez and the frontocerebellar circuit, in both of which the thalamus plays a key role. Shrinkage of the thalamus is more severe in alcoholics with Korsakoff's syndrome (KS) than in those without neurological complication (AL). In accordance with the gradient effect of thalamic abnormalities between AL and KS, the pattern of brain dysfunction in the Papez's circuit results in anterograde amnesia in KS and only mild-to-moderate episodic memory disorders in AL. On the opposite, dysfunction of the frontocerebellar circuit results in a similar pattern of working memory and executive deficits in the AL and KS. Several hypotheses, mutually compatible, can be drawn to explain that the severe thalamic shrinkage observed in KS has different consequences in the neuropsychological profile associated with the two brain networks. PMID:25108034

  20. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients

    PubMed Central

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  1. Positron Emission Tomography Reveals Abnormal Topological Organization in Functional Brain Network in Diabetic Patients.

    PubMed

    Qiu, Xiangzhe; Zhang, Yanjun; Feng, Hongbo; Jiang, Donglang

    2016-01-01

    Recent studies have demonstrated alterations in the topological organization of structural brain networks in diabetes mellitus (DM). However, the DM-related changes in the topological properties in functional brain networks are unexplored so far. We therefore used fluoro-D-glucose positron emission tomography (FDG-PET) data to construct functional brain networks of 73 DM patients and 91 sex- and age-matched normal controls (NCs), followed by a graph theoretical analysis. We found that both DM patients and NCs had a small-world topology in functional brain network. In comparison to the NC group, the DM group was found to have significantly lower small-world index, lower normalized clustering coefficients and higher normalized characteristic path length. Moreover, for diabetic patients, the nodal centrality was significantly reduced in the right rectus, the right cuneus, the left middle occipital gyrus, and the left postcentral gyrus, and it was significantly increased in the orbitofrontal region of the left middle frontal gyrus, the left olfactory region, and the right paracentral lobule. Our results demonstrated that the diabetic brain was associated with disrupted topological organization in the functional PET network, thus providing functional evidence for the abnormalities of brain networks in DM. PMID:27303259

  2. Ultrasound screening of periarticular soft tissue abnormality around metal-on-metal bearings.

    PubMed

    Nishii, Takashi; Sakai, Takashi; Takao, Masaki; Yoshikawa, Hideki; Sugano, Nobuhiko

    2012-06-01

    Although metal hypersensitivity or pseudotumors are concerns for metal-on-metal (MoM) bearings, detailed pathologies of patterns, severity, and incidence of periprosthetic soft tissue lesions are incompletely understood. We examined the potential of ultrasound for screening of periarticular soft tissue lesions around MoM bearings. Ultrasound examinations were conducted in 88 hips (79 patients) with MoM hip resurfacings or MoM total hip arthroplasties with a large femoral head. Four qualitative ultrasound patterns were shown, including normal pattern in 69 hips, joint-expansion pattern in 11 hips, cystic pattern in 5 hips, and mass pattern in 3 hips. Hips with the latter 3 abnormal patterns showed significantly higher frequency of clinical symptoms, without significant differences of sex, duration of implantation, head sizes, and cup abduction/anteversion angles, compared with hips with normal pattern. Ultrasound examination provides sensitive screening of soft tissue reactions around MoM bearings and may be useful in monitoring progression and defining treatment for periarticular soft tissue abnormalities. PMID:22047978

  3. Multimodality stereotactic brain tissue identification: the NASA smart probe project

    NASA Technical Reports Server (NTRS)

    Andrews, R.; Mah, R.; Aghevli, A.; Freitas, K.; Galvagni, A.; Guerrero, M.; Papsin, R.; Reed, C.; Stassinopoulos, D.

    1999-01-01

    Real-time tissue identification can benefit procedures such as stereotactic brain biopsy, functional neurosurgery and brain tumor excision. Optical scattering spectroscopy has been shown to be effective at discriminating cancer from noncancerous conditions in the colon, bladder and breast. The NASA Smart Probe extends the concept of 'optical biopsy' by using neural network techniques to combine the output from 3 microsensors contained within a cannula 2. 7 mm in diameter (i.e. the diameter of a stereotactic brain biopsy needle). Experimental data from 5 rats show the clear differentiation between tissues such as brain, nerve, fat, artery and muscle that can be achieved with optical scattering spectroscopy alone. These data and previous findings with other modalities such as (1) analysis of the image from a fiberoptic neuroendoscope and (2) the output from a microstrain gauge suggest the Smart Probe multiple microsensor technique shows promise for real-time tissue identification in neurosurgical procedures. Copyright 2000 S. Karger AG, Basel.

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

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27456312

  7. Supervised novelty detection in brain tissue classification with an application to white matter hyperintensities

    NASA Astrophysics Data System (ADS)

    Kuijf, Hugo J.; Moeskops, Pim; de Vos, Bob D.; Bouvy, Willem H.; de Bresser, Jeroen; Biessels, Geert Jan; Viergever, Max A.; Vincken, Koen L.

    2016-03-01

    Novelty detection is concerned with identifying test data that differs from the training data of a classifier. In the case of brain MR images, pathology or imaging artefacts are examples of untrained data. In this proof-of-principle study, we measure the behaviour of a classifier during the classification of trained labels (i.e. normal brain tissue). Next, we devise a measure that distinguishes normal classifier behaviour from abnormal behavior that occurs in the case of a novelty. This will be evaluated by training a kNN classifier on normal brain tissue, applying it to images with an untrained pathology (white matter hyperintensities (WMH)), and determine if our measure is able to identify abnormal classifier behaviour at WMH locations. For our kNN classifier, behaviour is modelled as the mean, median, or q1 distance to the k nearest points. Healthy tissue was trained on 15 images; classifier behaviour was trained/tested on 5 images with leave-one-out cross-validation. For each trained class, we measure the distribution of mean/median/q1 distances to the k nearest point. Next, for each test voxel, we compute its Z-score with respect to the measured distribution of its predicted label. We consider a Z-score >=4 abnormal behaviour of the classifier, having a probability due to chance of 0.000032. Our measure identified >90% of WMH volume and also highlighted other non-trained findings. The latter being predominantly vessels, cerebral falx, brain mask errors, choroid plexus. This measure is generalizable to other classifiers and might help in detecting unexpected findings or novelties by measuring classifier behaviour.

  8. Changes in Brain Tissue and Behavior Patterns Induced by Single Short-Term Fasting in Mice

    PubMed Central

    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. PMID:24224039

  9. Soya protein attenuates abnormalities of the renin-angiotensin system in adipose tissue from obese rats.

    PubMed

    Frigolet, María E; Torres, Nimbe; Tovar, Armando R

    2012-01-01

    Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities. PMID:21736766

  10. Age at First Episode Modulates Diagnosis-Related Structural Brain Abnormalities in Psychosis.

    PubMed

    Pina-Camacho, Laura; Del Rey-Mejías, Ángel; Janssen, Joost; Bioque, Miquel; González-Pinto, Ana; Arango, Celso; Lobo, Antonio; Sarró, Salvador; Desco, Manuel; Sanjuan, Julio; Lacalle-Aurioles, Maria; Cuesta, Manuel J; Saiz-Ruiz, Jerónimo; Bernardo, Miguel; Parellada, Mara

    2016-03-01

    Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis. PMID:26371339

  11. Abnormal brain activation during directed forgetting of negative memory in depressed patients.

    PubMed

    Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

    2016-01-15

    The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. PMID:26639452

  12. Co-localisation of abnormal brain structure and function in specific language impairment

    PubMed Central

    Badcock, Nicholas A.; Bishop, Dorothy V.M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior frontal cortex and decreased in the right caudate nucleus and superior temporal cortex bilaterally. The unaffected siblings also showed reduced grey matter in the caudate nucleus relative to controls. In an auditory covert naming task, the SLI group showed reduced activation in the left inferior frontal cortex, right putamen, and in the superior temporal cortex bilaterally. Despite spatially coincident structural and functional abnormalities in frontal and temporal areas, the relationships between structure and function in these regions were different. These findings suggest multiple structural and functional abnormalities in SLI that are differently associated with receptive and expressive language processing. PMID:22137677

  13. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults

    PubMed Central

    Virtanen, J K.; Siscovick, D S.; Longstreth, W T.; Kuller, L H.; Mozaffarian, D

    2008-01-01

    Objective: To investigate the association between fish consumption and subclinical brain abnormalities. Methods: In the population-based Cardiovascular Health Study, 3,660 participants age ≥65 underwent an MRI scan in 1992–1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. Results: After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish ≥3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54–1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Conclusions: Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits. GLOSSARY ARR = absolute risk reduction; BMI = body mass index; CHD = coronary heart disease; CHS = Cardiovascular Health Study; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FFQ = food frequency questionnaire; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; PUFA = polyunsaturated fatty acid; RR = relative risk. PMID:18678827

  14. Posterior brain white matter abnormalities in older adults with probable mild cognitive impairment

    PubMed Central

    Cooley, Sarah A.; Cabeen, Ryan P.; Laidlaw, David H.; Conturo, Thomas E.; Lane, Elizabeth M.; Heaps, Jodi M.; Bolzenius, Jacob D.; Baker, Laurie M.; Salminen, Lauren E.; Scott, Staci E.; Paul, Robert H.

    2014-01-01

    Objective Much of the mild cognitive impairment (MCI) neuroimaging literature has exclusively focused on regions associated with Alzheimer’s disease. Little research has examined white matter abnormalities of other brain regions, including those associated with visual processing, despite evidence that other brain abnormalities appear in these regions in early disease stages. Method Diffusion tensor imaging (DTI) was utilized to examine participants (n = 44) that completed baseline imaging as part of a longitudinal healthy aging study. Participants were divided into two groups based on scores from the Montreal Cognitive Assessment (MoCA), a brief screening tool for MCI. Participants who scored < 26 were defined as “probable MCI” while those who scored ≥ 26 were labled cognitively healthy. Two DTI indices were analyzed including fractional anisotropy (FA) and mean diffusivity (MD). DTI values for white matter in the lingual gyrus, cuneus, pericalcarine, fusiform gyrus and all four lobes were compared using MANOVA. Regression analyses examined the relationship between DTI indices and total MoCA score. Results Results revealed significantly lower FA in the probable MCI group in the cuneus, fusiform, pericalcarine and occipital lobe, and significantly higher MD in the temporal lobe. Fusiform FA and temporal lobe MD were significantly related to total MoCA score after accounting for age and education. Conclusions Results indicate that there are posterior white matter microstructural changes in individuals with probable MCI. These differences demonstrate that white matter abnormalities are evident among individuals with probable MCI in regions beyond those commonly associated with Alzheimer’s disease and anterior brain aging patterns. PMID:25523313

  15. Characterisation and modelling of brain tissue for surgical simulation.

    PubMed

    Mendizabal, A; Aguinaga, I; Sánchez, E

    2015-05-01

    Interactive surgical simulators capable of providing a realistic visual and haptic feedback to users are a promising technology for medical training and surgery planification. However, modelling the physical behaviour of human organs and tissues for surgery simulation remains a challenge. On the one hand, this is due to the difficulty to characterise the physical properties of biological soft tissues. On the other hand, the challenge still remains in the computation time requirements of real-time simulation required in interactive systems. Real-time surgical simulation and medical training must employ a sufficiently accurate and simple model of soft tissues in order to provide a realistic haptic and visual response. This study attempts to characterise the brain tissue at similar conditions to those that take place on surgical procedures. With this aim, porcine brain tissue is characterised, as a surrogate of human brain, on a rotational rheometer at low strain rates and large strains. In order to model the brain tissue with an adequate level of accuracy and simplicity, linear elastic, hyperelastic and quasi-linear viscoelastic models are defined. These models are simulated using the ABAQUS finite element platform and compared with the obtained experimental data. PMID:25676499

  16. Cerebral abnormalities in cocaine abusers: Demonstration by SPECT perfusion brain scintigraphy. Work in progress

    SciTech Connect

    Tumeh, S.S.; Nagel, J.S.; English, R.J.; Moore, M.; Holman, B.L. )

    1990-09-01

    Single photon emission computed tomography (SPECT) perfusion brain scans with iodine-123 isopropyl iodoamphetamine (IMP) were obtained in 12 subjects who acknowledged using cocaine on a sporadic to a daily basis. The route of cocaine administration varied from nasal to intravenous. Concurrent abuse of other drugs was also reported. None of the patients were positive for human immunodeficiency virus. Brain scans demonstrated focal defects in 11 subjects, including seven who were asymptomatic, and no abnormality in one. Among the findings were scattered focal cortical deficits, which were seen in several patients and which ranged in severity from small and few to multiple and large, with a special predilection for the frontal and temporal lobes. No perfusion deficits were seen on I-123 SPECT images in five healthy volunteers. Focal alterations in cerebral perfusion are seen commonly in asymptomatic drug users, and these focal deficits are readily depicted by I-123 IMP SPECT.

  17. Skeletal and Brain Abnormalities in Fucosidosis, a Rare Lysosomal Storage Disorder

    PubMed Central

    Malatt, Camille; Koning, Jeffrey L.; Naheedy, John

    2015-01-01

    Fucosidosis is a rare genetic lysosomal storage disorder caused by a deficiency in alpha- L-fucosidase. We present a case of a 4-year, 11-month-old girl with developmental delay, as well as skeletal and brain abnormalities as shown on X-ray and MRI. Her spinal X- rays demonstrated lumbar kyphosis and anterior beaking of lumbar vertebral bodies. Lower iliac segment constriction, increased angulation of the acetabular roof, and widening of the ribs were apparent on abdominal X-ray. Her brain MRI illustrated symmetric T1 hyperintensity and T2 hypointensity of the bilateral globi pallidi. The case report highlights clinical and imaging findings of this rare disease. PMID:26622931

  18. Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities.

    PubMed

    Driggers, Rita W; Ho, Cheng-Ying; Korhonen, Essi M; Kuivanen, Suvi; Jääskeläinen, Anne J; Smura, Teemu; Rosenberg, Avi; Hill, D Ashley; DeBiasi, Roberta L; Vezina, Gilbert; Timofeev, Julia; Rodriguez, Fausto J; Levanov, Lev; Razak, Jennifer; Iyengar, Preetha; Hennenfent, Andrew; Kennedy, Richard; Lanciotti, Robert; du Plessis, Adre; Vapalahti, Olli

    2016-06-01

    The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated. PMID:27028667

  19. Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study

    PubMed Central

    Cheung, Ning; Mosley, Thomas; Islam, Amirul; Kawasaki, Ryo; Sharrett, A. Richey; Klein, Ronald; Coker, Laura H.; Knopman, David S.; Shibata, Dean K.; Catellier, Diane

    2010-01-01

    Silent brain infarct and white matter lesions are common radiological findings associated with the risk of clinical stroke and dementia; however, our understanding of their underlying pathophysiology and risk factors remains limited. This study aimed to determine whether assessment of retinal microvascular abnormalities could provide prognostic information regarding the risk of brain infarct and white matter lesions on magnetic resonance imaging. This study is based on a subset of 810 middle-aged persons without clinical stroke or baseline magnetic resonance imaging infarct enrolled in the Atherosclerosis Risk in Communities Brain Magnetic Resonance Imaging Study, a prospective, population-based study. Participants had a baseline magnetic resonance imaging brain examination and retinal photography in 1993–1995, and returned for a repeat magnetic resonance imaging examination in 2004–2006. Magnetic resonance images were graded for presence of any cerebral infarct, infarct with lacunar characteristics and white matter lesions according to standardized protocols. Retinal photographs were graded for presence of retinopathy lesions and retinal arteriolar abnormalities following a standardized protocol. Over a median follow-up of 10.5 years, 164 (20.2%) participants developed cerebral infarct, 131 (16.2%) developed lacunar infarct, 182 (24.2%) developed new white matter lesions and 49 (6.1%) had evidence of white matter lesion progression. After adjusting for age, gender, race, cardiovascular risk factors and carotid intima-media thickness, retinopathy was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval 1.42–5.60) and lacunar infarct (odds ratio 3.19; 95% confidence interval: 1.56–6.50). Retinal arteriovenous nicking was associated with incident cerebral infarct (odds ratio 2.82; 95% confidence interval: 1.66–4.76), lacunar infarct (odds ratio 2.48; 95% confidence interval: 1.39–4.40) and white matter lesion incidence (odds

  20. Abnormal structural connectivity in the brain networks of children with hydrocephalus

    PubMed Central

    Yuan, Weihong; Holland, Scott K.; Shimony, Joshua S.; Altaye, Mekibib; Mangano, Francesco T.; Limbrick, David D.; Jones, Blaise V.; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C.

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  1. Abnormal structural connectivity in the brain networks of children with hydrocephalus.

    PubMed

    Yuan, Weihong; Holland, Scott K; Shimony, Joshua S; Altaye, Mekibib; Mangano, Francesco T; Limbrick, David D; Jones, Blaise V; Nash, Tiffany; Rajagopal, Akila; Simpson, Sarah; Ragan, Dustin; McKinstry, Robert C

    2015-01-01

    Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect

  2. Three-dimensional assessment of brain tissue morphology

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Germann, Marco; Jeanmonod, Daniel; Morel, Anne

    2006-08-01

    The microstructure of brain tissues becomes visible using different types of optical microscopy after the tissue sectioning. This preparation procedure introduces stress and strain in the anisotropic and inhomogeneous soft tissue slices, which are several 10 μm thick. Consequently, the three-dimensional dataset, generated out of the two-dimensional images with lateral submicrometer resolution, needs algorithms to correct the deformations, which can be significant for mellow tissue such as brain segments. The spatial resolution perpendicular to the slices is much worse with respect to the lateral sub-micrometer resolution. Therefore, we propose as complementary method the synchrotron-radiation-based micro computed tomography (SRμCT), which avoids any kind of preparation artifacts due to sectioning and histological processing and yields true micrometer resolution in the three orthogonal directions. The visualization of soft matter by the use of SRμCT, however, is often based on elaborate staining protocols, since the tissue exhibits (almost) the same x-ray absorption as the surrounding medium. Therefore, it is unexpected that human tissue from the pons and the medulla oblongata in phosphate buffer show several features such as the blood vessels and the inferior olivary nucleus without staining. The value of these tomograms lies especially in the precise non-rigid registration of the different sets of histological slices. Applications of this method to larger pieces of brain tissue, such as the human thalamus are planned in the context of stereotactic functional neurosurgery.

  3. C21orf5, a human candidate gene for brain abnormalities and mental retardation in Down syndrome.

    PubMed

    Rachidi, M; Lopes, C; Delezoide, A-L; Delabar, J M

    2006-01-01

    Mental retardation represents the more invalidating pathological aspect of trisomy 21 and has a hard impact on public health. The dosage imbalance of chromosome 21 genes could be the cause of neurological alterations and mental retardation seen in Down syndrome. We studied C21orf5 that we have demonstrated to be overexpressed in Down syndrome tissues, as a candidate gene for trisomy 21. A new optical technology (Rachidi et al., 2000) was used to compare signal intensity and cell density in presumptive embryonic brain compartments, at their boundaries and in higher specialized brain centres during fetal lifespan. We showed a developmentally regulated transcriptional activity of C21orf5 and a regional and cellular specific distribution of gene transcripts during human embryonic and fetal development. A wide but differential expression was detected in the nervous system during embryogenesis with a relatively lower level in the forebrain than in the midbrain and hindbrain and the highest transcription intensity in the future cerebellum. This developmentally regulated expression is maintained during post-embryogenesis and evolves selectively in fetal cerebral, hippocampal and cerebellar areas. Differential and cellular specificity were detected in hippocampus with higher C21orf5 mRNA level in the pyramidal cells compared to granular cells of the dentate gyrus. The expression pattern detected in cortical and cerebellar structures correlates well to the altered cortical lamination and to the lower size of the cerebellum observed in Down syndrome patients. In addition, the patterned differential expression detected in the medial temporal-lobe system, including hippocampal formation and perirhinal cortex, working as control centres of the memory circuits and involved in cognitive processes and memory storage, also corresponds to abnormal brain regions seen in Down syndrome patients. The C21orf5 selective expression in the key brain structures for learning and memory

  4. Structural abnormalities of the brain in schizophrenia: sex differences in the Cantabria First Episode of Schizophrenia Study.

    PubMed

    Vázquez-Barquero, J L; Cuesta Núñez, M J; Quintana Pando, F; de la Varga, M; Herrera Castanedo, S; Dunn, G

    1995-11-01

    This paper examines structural brain abnormalities, as evaluated by the CT scan, in first episodes of schizophrenia and their association with sociodemographic, diagnostic and clinical variables. The investigation included all patients with a first episode of schizophrenia who, over a 2-year period, made contact with any of the public mental health services of the Autonomous Region of Cantabria in Northern Spain. Diagnostic and clinical characteristics were evaluated through the use of the Spanish version of the Present State Examination (PSE-9) and the Scales for the Assessment of Positive and Negative Symptoms (SANS and SAPS respectively). The study demonstrated the presence of structural brain abnormalities in this sample of first episode schizophrenics. These abnormalities were mainly expressed in the presence of larger VBR for schizophrenic patients than in the controls, these findings being more marked in women than in men. We failed to reveal, however, any evidence of an association of these brain abnormalities with diagnostic or clinical characteristics. PMID:8637954

  5. Measuring the local electrical conductivity of human brain tissue

    NASA Astrophysics Data System (ADS)

    Akhtari, M.; Emin, D.; Ellingson, B. M.; Woodworth, D.; Frew, A.; Mathern, G. W.

    2016-02-01

    The electrical conductivities of freshly excised brain tissues from 24 patients were measured. The diffusion-MRI of the hydrogen nuclei of water molecules from regions that were subsequently excised was also measured. Analysis of these measurements indicates that differences between samples' conductivities are primarily due to differences of their densities of solvated sodium cations. Concomitantly, the sample-to-sample variations of their diffusion constants are relatively small. This finding suggests that non-invasive in-vivo measurements of brain tissues' local sodium-cation density can be utilized to estimate its local electrical conductivity.

  6. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease

    PubMed Central

    Tian, Junzhang; Dong, Jianwei; He, Jinlong; Zhan, Wenfeng; Xu, Lijuan; Xu, Yikai; Jiang, Guihua

    2016-01-01

    Purpose To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD) and examine the relationship between brain microstructure and physiological indictors in the disease. Materials and Methods Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18–61 years) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22–58 years). A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients. Results Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM) but also gray matter (GM) regions, as characterized by decreased fractional anisotropy (FA) and increased mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part) in the patients. Conclusion Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease. PMID:27227649

  7. Tourette's syndrome: a neurochemical analysis of postmortem cortical brain tissue.

    PubMed

    Singer, H S; Hahn, I H; Krowiak, E; Nelson, E; Moran, T

    1990-04-01

    Postmortem frontal, temporal, and occipital regions of the brain from adult patients who had a diagnosis of Tourette's syndrome were analyzed for neurochemical alterations. In 3 of 4 TS-affected brains, the concentration of adenosine 3',5'-monophosphate (cyclic AMP) was reduced in all brain regions evaluated. This diminution in cyclic AMP was not associated with a significant change in the activity of the synthesizing enzyme, adenylate cyclase. No significant differences were identified for the neurotransmitter-synthesizing enzymes choline acetyltransferase and glutamate decarboxylase. Concentrations of dopamine, norepinephrine, and the serotonin metabolite 5-hydroxyindoleacetic acid were not altered. Postsynaptic receptor-binding activity for muscarinic cholinergic ([3H]quinuclidinyl benzilate) and beta receptors ([125I]iodocyanopindolol) showed no generalized impairment. It is suggested that symptoms of Tourette's syndrome might be related to an abnormality within a second messenger system. PMID:1972320

  8. Abnormal White Matter Blood-Oxygen-Level-Dependent Signals in Chronic Mild Traumatic Brain Injury.

    PubMed

    Astafiev, Serguei V; Shulman, Gordon L; Metcalf, Nicholas V; Rengachary, Jennifer; MacDonald, Christine L; Harrington, Deborah L; Maruta, Jun; Shimony, Joshua S; Ghajar, Jamshid; Diwakar, Mithun; Huang, Ming-Xiong; Lee, Roland R; Corbetta, Maurizio

    2015-08-15

    Concussion, or mild traumatic brain injury (mTBI), can cause persistent behavioral symptoms and cognitive impairment, but it is unclear if this condition is associated with detectable structural or functional brain changes. At two sites, chronic mTBI human subjects with persistent post-concussive symptoms (three months to five years after injury) and age- and education-matched healthy human control subjects underwent extensive neuropsychological and visual tracking eye movement tests. At one site, patients and controls also performed the visual tracking tasks while blood-oxygen-level-dependent (BOLD) signals were measured with functional magnetic resonance imaging. Although neither neuropsychological nor visual tracking measures distinguished patients from controls at the level of individual subjects, abnormal BOLD signals were reliably detected in patients. The most consistent changes were localized in white matter regions: anterior internal capsule and superior longitudinal fasciculus. In contrast, BOLD signals were normal in cortical regions, such as the frontal eye field and intraparietal sulcus, that mediate oculomotor and attention functions necessary for visual tracking. The abnormal BOLD signals accurately differentiated chronic mTBI patients from healthy controls at the single-subject level, although they did not correlate with symptoms or neuropsychological performance. We conclude that subjects with persistent post-concussive symptoms can be identified years after their TBI using fMRI and an eye movement task despite showing normal structural MRI and DTI. PMID:25758167

  9. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study

    PubMed Central

    Zhong, Wei-Jia; Zhou, Zhi-Ming; Zhao, Jian-Nong; Wu, Wei; Guo, Da-Jing

    2016-01-01

    PURPOSE We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). METHODS A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. RESULTS Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. CONCLUSION ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE. PMID:26742646

  10. MRI of brain tissue oxygen tension under hyperbaric conditions.

    PubMed

    Muir, Eric R; Cardenas, Damon P; Duong, Timothy Q

    2016-06-01

    The brain depends on a continuous supply of oxygen to maintain its structural and functional integrity. This study measured T1 from MRI under normobaric air, normobaric oxygen, hyperbaric air, and hyperbaric oxygen (HBO) conditions as a marker of tissue pO2 since dissolved molecular oxygen acts as an endogenous contrast agent. Brain tissue T1 decreased corresponding to increased pO2 with increasing inhaled oxygen concentrations, and tissue oxygenation was estimated from the T1 changes between different inhaled oxygen levels. Tissue pO2 difference maps between different oxygen conditions showed heterogeneous pO2 changes in the brain. MRI-derived tissue pO2 was markedly lower than the arterial pO2 but was slightly higher than venous pO2. Additionally, for comparison with published extracellular tissue pO2 data obtained using oxygen electrodes and other invasive techniques, a model was used to estimate extracellular and intracellular pO2 from the MRI-derived mean tissue pO2. This required multiple assumptions, and so the effects of the assumptions and parameters used in modeling brain pO2 were evaluated. MRI-derived pO2 values were strongly dependent on assumptions about the extra- and intracellular compartments but were relatively less sensitive to variations in the relaxivity constant of oxygen and contribution from oxygen in the cerebral blood compartment. This approach may prove useful in evaluating tissue oxygenation in disease states such as stroke. PMID:27033683

  11. Effects of hyperbaric oxygen on eye tracking abnormalities in males after mild traumatic brain injury.

    PubMed

    Cifu, David X; Hoke, Kathy W; Wetzel, Paul A; Wares, Joanna R; Gitchel, George; Carne, William

    2014-01-01

    The effects of hyperbaric oxygen (HBO2) on eye movement abnormalities in 60 military servicemembers with at least one mild traumatic brain injury (TBI) from combat were examined in a single-center, randomized, double-blind, sham-controlled, prospective study at the Naval Medicine Operational Training Center. During the 10 wk of the study, each subject was delivered a series of 40, once a day, hyperbaric chamber compressions at a pressure of 2.0 atmospheres absolute (ATA). At each session, subjects breathed one of three preassigned oxygen fractions (10.5%, 75%, or 100%) for 1 h, resulting in an oxygen exposure equivalent to breathing either surface air, 100% oxygen at 1.5 ATA, or 100% oxygen at 2.0 ATA, respectively. Using a standardized, validated, computerized eye tracking protocol, fixation, saccades, and smooth pursuit eye movements were measured just prior to intervention and immediately postintervention. Between and within groups testing of pre- and postintervention means revealed no significant differences on eye movement abnormalities and no significant main effect for HBO2 at either 1.5 ATA or 2.0 ATA equivalent compared with the sham-control. This study demonstrated that neither 1.5 nor 2.0 ATA equivalent HBO2 had an effect on postconcussive eye movement abnormalities after mild TBI when compared with a sham-control. PMID:25436771

  12. Mechanical response of brain tissue under blast loading.

    PubMed

    Laksari, Kaveh; Sadeghipour, Keyanoush; Darvish, Kurosh

    2014-04-01

    In this study, a framework for understanding the propagation of stress waves in brain tissue under blast loading has been developed. It was shown that tissue nonlinearity and rate dependence are the key parameters in predicting the mechanical behavior under such loadings, as they determine whether traveling waves could become steeper and eventually evolve into shock discontinuities. To investigate this phenomenon, in the present study, brain tissue has been characterized as a quasi-linear viscoelastic (QLV) material and a nonlinear constitutive model has been developed for the tissue that spans from medium loading rates up to blast rates. It was shown that development of shock waves is possible inside the head in response to high rate compressive pressure waves. Finally, it was argued that injury to the nervous tissue at the microstructural level could be partly attributed to the high stress gradients with high rates generated at the shock front and this was proposed as a mechanism of injury in brain tissue. PMID:24457112

  13. The nature of white matter abnormalities in blast-related mild traumatic brain injury

    PubMed Central

    Hayes, Jasmeet P.; Miller, Danielle R.; Lafleche, Ginette; Salat, David H.; Verfaellie, Mieke

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having

  14. The nature of white matter abnormalities in blast-related mild traumatic brain injury.

    PubMed

    Hayes, Jasmeet P; Miller, Danielle R; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2015-01-01

    Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having

  15. Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

    PubMed Central

    Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

    2013-01-01

    Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

  16. Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

    PubMed Central

    Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

    2016-01-01

    Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

  17. Sensory neuron-specific sodium channel SNS is abnormally expressed in the brains of mice with experimental allergic encephalomyelitis and humans with multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Black, Joel A.; Dib-Hajj, Sulayman; Baker, David; Newcombe, Jia; Cuzner, M. Louise; Waxman, Stephen G.

    2000-10-01

    Clinical abnormalities in multiple sclerosis (MS) have classically been considered to be caused by demyelination and/or axonal degeneration; the possibility of molecular changes in neurons, such as the deployment of abnormal repertoires of ion channels that would alter neuronal electrogenic properties, has not been considered. Sensory Neuron-Specific sodium channel SNS displays a depolarized voltage dependence, slower activation and inactivation kinetics, and more rapid recovery from inactivation than classical "fast" sodium channels. SNS is selectively expressed in spinal sensory and trigeminal ganglion neurons within the peripheral nervous system and is not expressed within the normal brain. Here we show that sodium channel SNS mRNA and protein, which are not present within the cerebellum of control mice, are expressed within cerebellar Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. We also demonstrate SNS mRNA and protein expression within Purkinje cells from tissue obtained postmortem from patients with MS, but not in control subjects with no neurological disease. These results demonstrate a change in sodium channel expression in neurons within the brain in an animal model of MS and in humans with MS and suggest that abnormal patterns of neuronal ion channel expression may contribute to clinical abnormalities such as ataxia in these disorders.

  18. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

    PubMed

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W

    2008-11-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children. PMID:18550243

  19. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice.

    PubMed

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-04-14

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  20. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

    PubMed Central

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-01-01

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  1. Multicenter Study of Brain Volume Abnormalities in Children and Adolescent-Onset Psychosis

    PubMed Central

    Reig, Santiago; Parellada, Mara; Castro-Fornieles, Josefina; Janssen, Joost; Moreno, Dolores; Baeza, Inmaculada; Bargalló, Nuria; González-Pinto, Ana; Graell, Montserrat; Ortuño, Felipe; Otero, Soraya; Arango, Celso; Desco, Manuel

    2011-01-01

    The goal of the study is to determine the extent of structural brain abnormalities in a multicenter sample of children and adolescents with a recent-onset first episode of psychosis (FEP), compared with a sample of healthy controls. Total brain and lobar volumes and those of gray matter (GM), white matter, and cerebrospinal fluid (CSF) were measured in 92 patients with a FEP and in 94 controls, matched for age, gender, and years of education. Male patients (n = 64) showed several significant differences when compared with controls (n = 61). GM volume in male patients was reduced in the whole brain and in frontal and parietal lobes compared with controls. Total CSF volume and frontal, temporal, and right parietal CSF volumes were also increased in male patients. Within patients, those with a further diagnosis of “schizophrenia” or “other psychosis” showed a pattern similar to the group of all patients relative to controls. However, bipolar patients showed fewer differences relative to controls. In female patients, only the schizophrenia group showed differences relative to controls, in frontal CSF. GM deficit in male patients with a first episode correlated with negative symptoms. Our study suggests that at least part of the GM deficit in children and adolescent-onset schizophrenia and in other psychosis occurs before onset of the first positive symptoms and that, contrary to what has been shown in children-onset schizophrenia, frontal GM deficits are probably present from the first appearance of positive symptoms in children and adolescents. PMID:20478821

  2. Neurological Gait Abnormalities Moderate the Functional Brain Signature of the Posture First Hypothesis.

    PubMed

    Holtzer, Roee; Verghese, Joe; Allali, Gilles; Izzetoglu, Meltem; Wang, Cuiling; Mahoney, Jeannette R

    2016-03-01

    The posture first hypothesis suggests that under dual-task walking conditions older adults prioritize gait over cognitive task performance. Functional neural confirmation of this hypothesis, however, is lacking. Herein, we determined the functional neural correlates of the posture first hypothesis and hypothesized that the presence of neurological gait abnormalities (NGA) would moderate associations between brain activations, gait and cognitive performance. Using functional near-infrared spectroscopy we assessed changes in oxygenated hemoglobin levels in the pre-frontal cortex (PFC) during normal walk and walk while talk (WWT) conditions in a large cohort of non-demented older adults (n = 236; age = 75.5 ± 6.49 years; female = 51.7 %). NGA were defined as central (due to brain diseases) or peripheral (neuropathic gait) following a standardized neurological examination protocol. Double dissociations between brain activations and behavior emerged as a function of NGA. Higher oxygenation levels during WWT were related to better cognitive performance (estimate = 0.145; p < 0.001) but slower gait velocity (estimate = -6.336, p < 0.05) among normals. In contrast, higher oxygenation levels during WWT among individuals with peripheral NGA were associated with worse cognitive performance (estimate = -0.355; p < 0.001) but faster gait velocity (estimate = 14.855; p < 0.05). Increased activation in the PFC during locomotion may have a compensatory function that is designed to support gait among individuals with peripheral NGA. PMID:26613725

  3. Multidimensional morphometric 3D MRI analyses for detecting brain abnormalities in children: impact of control population.

    PubMed

    Wilke, Marko; Rose, Douglas F; Holland, Scott K; Leach, James L

    2014-07-01

    Automated morphometric approaches are used to detect epileptogenic structural abnormalities in 3D MR images in adults, using the variance of a control population to obtain z-score maps in an individual patient. Due to the substantial changes the developing human brain undergoes, performing such analyses in children is challenging. This study investigated six features derived from high-resolution T1 datasets in four groups: normal children (1.5T or 3T data), normal clinical scans (3T data), and patients with structural brain lesions (3T data), with each n = 10. Normative control data were obtained from the NIH study on normal brain development (n = 401). We show that control group size substantially influences the captured variance, directly impacting the patient's z-scores. Interestingly, matching on gender does not seem to be beneficial, which was unexpected. Using data obtained at higher field scanners produces slightly different base rates of suprathreshold voxels, as does using clinically derived normal studies, suggesting a subtle but systematic effect of both factors. Two approaches for controlling suprathreshold voxels in a multidimensional approach (combining features and requiring a minimum cluster size) were shown to be substantial and effective in reducing this number. Finally, specific strengths and limitations of such an approach could be demonstrated in individual cases. PMID:25050423

  4. [A brain tissue bank in a neuropathology laboratory. Basic methodology].

    PubMed

    Rivas, E; Teijeira, S; Tardio, A; Fachal, C; Quintáns, B; Navarro, C

    2003-12-01

    The Meixoeiro Hospital Brain Bank (BB) was established at the end of 2002. A BB is a tissue collection and storage system, established under the best conditions to carry out prospective morphological, biochemical or molecular studies. The BB should ideally be supported by a donor program, although samples may also be obtained from autopsy material from patients with neurodegenerative diseases. Recruitment of control cases from brains without neurological diseases is basic. The main goal of a BB is to provide brain tissue for research. Each case requires accurate clinical data, a definite diagnosis and optimal conditions of tissue preservation. The use of protocols to standardize the handling and processing of tissues, data recruitment and neuropathological diagnosis is fundamental to assure the quality and homogeneity of samples. Close collaboration between neuropathologists, neurologists and other specialists is essential in all the process. Although important advances in the tissue banking field have been achieved, the number of donors in Spain still remains low. Stronger institutional support as well as public awareness through better diffusion of the information is necessary to increase the number of donors and improve BB development. PMID:14648346

  5. Novel SLC5A2 mutation contributes to familial renal glucosuria: Abnormal expression in renal tissues

    PubMed Central

    Yu, Lei; Hou, Ping; Liu, Guo-Ping; Zhang, Hong

    2016-01-01

    Familial renal glucosuria (FRG) is characterized by persistent glucosuria in the presence of normal serum glucose concentrations, while other impairments of tubular function are absent. Mutations in the sodium-glucose co-transporter 2 (SLC5A2) gene have been found to be responsible for FRG. However, direct evidence for the presence of SLC5A2 mutant in renal tissues is very rare. In previous studies, a non-sense mutation (c.1320 G>A:p.W440X) that would cause premature termination of the protein was found. However, the effects in the renal tissues were not reported. In the current study, a patient with FRG and a urinary glucose excretion rate of 8.3 g/day is described, for whom a novel missense mutation (c.1319G>A:p.W440X) was revealed by sequencing. Furthermore, in the immunofluorescence examination of a renal biopsy specimen, SLC5A2 was detected in the apical side of the proximal convoluted tubule, discontinuously decreased in comparison with that in normal and disease controls. The results imply that both wild-type SLC5A2 and mutant SLC5A2 with abnormal distribution were expressed in the renal tissues, and that the reduction of SLC5A2 expression and function were due to the c.1319G>A:p.W440X mutation. The current study provides valuable clues regarding the SLC5A2 molecule from genotype to phenotype in families affected by FRG.

  6. Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

    2015-03-01

    Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

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

    PubMed

    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

  8. Hypercatabolism of normal IgG; an unexplained immunoglobulin abnormality in the connective tissue diseases

    PubMed Central

    Wochner, R. Dean

    1970-01-01

    The metabolism of radioiodinated IgG was studied in a series of 42 patients with connective tissue diseases (16 systemic lupus erythematosus, nine rheumatoid arthritis, five polymyositis, five vasculitis, and seven miscellaneous diagnoses). Fractional catabolic rates were increased and survival half-lives were shortened in all diagnostic categories indicating hypercatabolism of IgG. This hypercatabolism was masked by increased IgG synthesis, resulting in elevated serum concentrations of IgG in patients with systemic lupus erythematosus and rheumatoid arthritis and in generally normal concentrations in the others. The metabolism of iodinated IgM was also studied in eight patients with systemic lupus erythematosus, in seven with rheumatoid arthritis, and in 12 controls. The fractional catabolic rates were normal in both groups of patients. Serum concentrations of both IgM and IgA were moderately elevated in all diagnostic categories. Serum albumin metabolism was entirely normal in the nine subjects studied who were not receiving corticosteroids; in three who were receiving them, moderate hypercatabolism was observed. The hypercatabolism of IgG could not be accounted for by factors previously known to alter IgG metabolism. It was not observed in 15 patients with other chronic, inflammatory diseases and was not explained by concomitant administration of adrenal corticosteroids to some patients. Identical results were obtained whether the IgG was obtained from a patient himself or from a normal donor, demonstrating that the hypercatabolism is a host defect and not an abnormality of the protein. Thus, patients with connective tissue disease of several different diagnostic categories have been shown to have an unexplained immunoglobulin abnormality: they catabolize normal IgG at an accelerated rate. PMID:5415673

  9. Neonatal brain abnormalities associated with autism spectrum disorder in children born very preterm.

    PubMed

    Ure, Alexandra M; Treyvaud, Karli; Thompson, Deanne K; Pascoe, Leona; Roberts, Gehan; Lee, Katherine J; Seal, Marc L; Northam, Elisabeth; Cheong, Jeanie L; Hunt, Rod W; Inder, Terrie; Doyle, Lex W; Anderson, Peter J

    2016-05-01

    Very preterm (VP) survivors are at increased risk of autism spectrum disorder (ASD) compared with term-born children. This study explored whether neonatal magnetic resonance (MR) brain features differed in VP children with and without ASD at 7 years. One hundred and seventy-two VP children (<30 weeks' gestation or <1250 g birth weight) underwent structural brain MR scans at term equivalent age (TEA; 40 weeks' gestation ±2 weeks) and were assessed for ASD at 7 years of age. The presence and severity of white matter, cortical gray matter, deep nuclear gray matter, and cerebellar abnormalities were assessed, and total and regional brain volumes were measured. ASD was diagnosed using a standardized parent report diagnostic interview and confirmed via an independent assessment. Eight VP children (4.7%) were diagnosed with ASD. Children with ASD had more cystic lesions in the cortical white matter at TEA compared with those without ASD (odds ratio [OR] 8.7, 95% confidence interval [CI] 1.5, 51.3, P = 0.02). There was also some evidence for smaller cerebellar volumes in children with ASD compared with those without ASD (OR = 0.82, CI = 0.66, 1.00, P = 0.06). Overall, the results suggest that VP children with ASD have different brain structure in the neonatal period compared with those who do not have ASD. Autism Res 2016, 9: 543-552. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26442616

  10. Brain and Cognition Abnormalities in Long-Term Anabolic-Androgenic Steroid Users

    PubMed Central

    Kaufman, Marc J.; Janes, Amy C.; Hudson, James I.; Brennan, Brian P.; Kanayama, Gen; Kerrigan, Andrew R.; Jensen, J. Eric; Pope, Harrison G.

    2015-01-01

    Background Anabolic-androgenic steroid (AAS) use is associated with psychiatric symptoms including increased aggression as well as with cognitive dysfunction. The brain effects of long-term AAS use have not been assessed in humans. Methods This multimodal magnetic resonance imaging study of the brain compared 10 male weightlifters reporting long-term AAS use with 10 age-matched weightlifters reporting no AAS exposure. Participants were administered visuospatial memory tests and underwent neuroimaging. Brain volumetric analyses were performed; resting-state fMRI functional connectivity (rsFC) was evaluated using a region-of-interest analysis focused on the amygdala; and dorsal anterior cingulate cortex (dACC) metabolites were quantified by proton magnetic resonance spectroscopy (MRS). Results AAS users had larger right amygdala volumes than nonusers (P=0.002) and reduced rsFC between right amygdala and frontal, striatal, limbic, hippocampal, and visual cortical areas. Left amygdala volumes were slightly larger in AAS users (P=0.061) but few group differences were detected in left amygdala rsFC. AAS users also had lower dACC scyllo-inositol levels (P=0.004) and higher glutamine/glutamate ratios (P=0.028), possibly reflecting increased glutamate turnover. On a visuospatial cognitive task, AAS users performed more poorly than nonusers, with the difference approaching significance (P=0.053). Conclusions Long-term AAS use is associated with right amygdala enlargement and reduced right amygdala rsFC with brain areas involved in cognitive control and spatial memory, which could contribute to the psychiatric effects and cognitive dysfunction associated with AAS use. The MRS abnormalities we detected could reflect enhanced glutamate turnover and increased vulnerability to neurotoxic or neurodegenerative processes, which could contribute to AAS-associated cognitive dysfunction. PMID:25986964

  11. Transistor needle chip for recording in brain tissue

    NASA Astrophysics Data System (ADS)

    Felderer, Florian; Fromherz, Peter

    2011-07-01

    We report on a proof-of-principle experiment for the direct interfacing of transistors with intact brain tissue. A transistor needle chip (TNC) with a TiO2 surface is fabricated from a silicon-on-insulator wafer and impaled into an acute brain slice cut from hippocampus of the rat. While stimulating the Schaffer collateral, a local field potential is recorded in stratum radiatum of the CA1 region with field-effect transistors in the central part of the slice where the tissue is not damaged by the cutting process. After the impalement, the signal amplitude is small. Within an hour, it increases to a stable level around -2 mV as is recorded with a conventional micropipette electrode. The recovery indicates that the tissue is able to adapt to the impaled chip. Upon repeated impalements at the same position, the large signal is observed without delay. A profile of the transistor signal across the slice is due to the boundary conditions of a brain slice with both surfaces held near ground potential. The experiments with the TNC prototype are a basis for the development of silicon needle chips with a large multi-transistor array (MTA) for applications in brain-computer interfacing.

  12. Functional Tissue Pulsatility Imaging of the Brain during Visual Stimulation

    PubMed Central

    Kucewicz, John C.; Dunmire, Barbrina; Leotta, Daniel F.; Panagiotides, Heracles; Paun, Marla; Beach, Kirk W.

    2007-01-01

    Functional tissue pulsatility imaging (fTPI) is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility due to changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, non-ultrasound technology for measuring expansion of a whole limb or body part due to perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow and relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile “plethysmographic” signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate Analysis of Variance (MANOVA) was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 out 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex. PMID:17346872

  13. Apert and Crouzon syndromes-Cognitive development, brain abnormalities, and molecular aspects.

    PubMed

    Fernandes, Marilyse B L; Maximino, Luciana P; Perosa, Gimol B; Abramides, Dagma V M; Passos-Bueno, Maria Rita; Yacubian-Fernandes, Adriano

    2016-06-01

    Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain-of-function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain-of-function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940-2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS). © 2016 Wiley Periodicals, Inc. PMID:27028366

  14. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    PubMed Central

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  15. Bilateral brain abnormalities associated with dominantly inherited verbal and orofacial dyspraxia.

    PubMed

    Belton, Emma; Salmond, Claire H; Watkins, Kate E; Vargha-Khadem, Faraneh; Gadian, David G

    2003-03-01

    The KE family is a large three-generational pedigree in which half of the members suffer from a verbal and orofacial dyspraxia in association with a point mutation in the FOXP2 gene. This report extends previous voxel-based morphometric analyses of magnetic resonance imaging (MRI) scans (Watkins et al. [2002] Brain 125:465-478) using a bilateral conjunction analysis. This searches specifically for areas of grey matter density that differ bilaterally in the affected members compared with both matched controls and the unaffected family members. 3-D T1-weighted MRI datasets of 17 family members (10 affected, 7 unaffected) and matched controls were compared. The most significant findings were reduced grey matter density bilaterally in the caudate nucleus, the cerebellum, and the left and right inferior frontal gyrus in the affected members. In addition, increased grey matter density was found bilaterally in the planum temporale. These results confirm that a point mutation in FOXP2 is associated with several bilateral grey matter abnormalities in both motor and language related regions. The results also demonstrate the advantages of using a conjunction analysis when bilateral abnormalities are suspected. PMID:12599277

  16. Mathematical Difficulties and White Matter Abnormalities in Subacute Pediatric Mild Traumatic Brain Injury.

    PubMed

    Van Beek, Leen; Ghesquière, Pol; Lagae, Lieven; De Smedt, Bert

    2015-10-15

    Mathematical difficulties have been documented following pediatric mild traumatic brain injury (mTBI), yet a precise characterization of these impairments and their neural correlates is currently unavailable. We aimed to characterize these impairments by comparing behavioral and neuroimaging (i.e., diffusion tensor imaging [DTI]) outcomes from children with subacute mTBI to typically-developing controls. Twenty subacute pediatric mTBI patients and 20 well-matched controls underwent cognitive assessment and DTI examination. DTI tractography was used to detect white matter abnormalities in the corpus callosum (CC) and superior and inferior longitudinal fasciculi; these tracts are involved in mathematical performance and they are often damaged after mTBI. Behavioral results revealed that children with mTBI performed significantly more poorly on rapid apprehension of small numbers of objects (or "subitizing"), processing of non-symbolic numerosities, and procedural problem solving. These group differences were explained by differences in visuospatial working memory, which suggests that the observed mathematical difficulties may be a consequence of impairments in visuospatial abilities. DTI analysis revealed subtle group differences in the CC genu and splenium (i.e., higher fractional anisotropy and lower mean and radial diffusivity in children with mTBI) but the observed white matter abnormalities of the CC were not significantly associated with the observed mathematical difficulties in the mTBI patients. PMID:25915107

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

    PubMed Central

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

    2013-01-01

    The New South Wales Tissue Resource Centre (NSW TRC) at the University of Sydney, Australia is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain disease (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951–61) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539–52). PMID:24033426

  18. Automatic Segmentation of Eight Tissue Classes in Neonatal Brain MRI

    PubMed Central

    Anbeek, Petronella; Išgum, Ivana; van Kooij, Britt J. M.; Mol, Christian P.; Kersbergen, Karina J.; Groenendaal, Floris; Viergever, Max A.; de Vries, Linda S.; Benders, Manon J. N. L.

    2013-01-01

    Purpose Volumetric measurements of neonatal brain tissues may be used as a biomarker for later neurodevelopmental outcome. We propose an automatic method for probabilistic brain segmentation in neonatal MRIs. Materials and Methods In an IRB-approved study axial T1- and T2-weighted MR images were acquired at term-equivalent age for a preterm cohort of 108 neonates. A method for automatic probabilistic segmentation of the images into eight cerebral tissue classes was developed: cortical and central grey matter, unmyelinated and myelinated white matter, cerebrospinal fluid in the ventricles and in the extra cerebral space, brainstem and cerebellum. Segmentation is based on supervised pixel classification using intensity values and spatial positions of the image voxels. The method was trained and evaluated using leave-one-out experiments on seven images, for which an expert had set a reference standard manually. Subsequently, the method was applied to the remaining 101 scans, and the resulting segmentations were evaluated visually by three experts. Finally, volumes of the eight segmented tissue classes were determined for each patient. Results The Dice similarity coefficients of the segmented tissue classes, except myelinated white matter, ranged from 0.75 to 0.92. Myelinated white matter was difficult to segment and the achieved Dice coefficient was 0.47. Visual analysis of the results demonstrated accurate segmentations of the eight tissue classes. The probabilistic segmentation method produced volumes that compared favorably with the reference standard. Conclusion The proposed method provides accurate segmentation of neonatal brain MR images into all given tissue classes, except myelinated white matter. This is the one of the first methods that distinguishes cerebrospinal fluid in the ventricles from cerebrospinal fluid in the extracerebral space. This method might be helpful in predicting neurodevelopmental outcome and useful for evaluating neuroprotective clinical

  19. Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

    SciTech Connect

    Hua Chiaho; Wu Shengjie; Chemaitilly, Wassim; Lukose, Renin C.; Merchant, Thomas E.

    2012-11-15

    Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.

  20. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder.

    PubMed

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R; Fan, Jin

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  1. Structural brain abnormalities in the frontostriatal system and cerebellum in pedophilia.

    PubMed

    Schiffer, Boris; Peschel, Thomas; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Krueger, Tillmann H C

    2007-11-01

    Even though previous neuropsychological studies and clinical case reports have suggested an association between pedophilia and frontocortical dysfunction, our knowledge about the neurobiological mechanisms underlying pedophilia is still fragmentary. Specifically, the brain morphology of such disorders has not yet been investigated using MR imaging techniques. Whole brain structural T1-weighted MR images from 18 pedophile patients (9 attracted to males, 9 attracted to females) and 24 healthy age-matched control subjects (12 hetero- and 12 homosexual) from a comparable socioeconomic stratum were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. Compared to the homosexual and heterosexual control subjects, pedophiles showed decreased gray matter volume in the ventral striatum (also extending into the nucl. accumbens), the orbitofrontal cortex and the cerebellum. These observations further indicate an association between frontostriatal morphometric abnormalities and pedophilia. In this respect these findings may support the hypothesis that there is a shared etiopathological mechanism in all obsessive-compulsive spectrum disorders. PMID:16876824

  2. Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

    PubMed Central

    Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

    2014-01-01

    Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

  3. Chemoselective imaging of mouse brain tissue via multiplex CARS microscopy.

    PubMed

    Pohling, Christoph; Buckup, Tiago; Pagenstecher, Axel; Motzkus, Marcus

    2011-08-01

    The fast and reliable characterization of pathological tissue is a debated topic in the application of vibrational spectroscopy in medicine. In the present work we apply multiplex coherent anti-Stokes Raman scattering (MCARS) to the investigation of fresh mouse brain tissue. The combination of imaginary part extraction followed by principal component analysis led to color contrast between grey and white matter as well as layers of granule and Purkinje cells. Additional quantitative information was obtained by using a decomposition algorithm. The results perfectly agree with HE stained references slides prepared separately making multiplex CARS an ideal approach for chemoselective imaging. PMID:21833351

  4. Abnormal Brain Areas Common to the Focal Epilepsies: Multivariate Pattern Analysis of fMRI.

    PubMed

    Pedersen, Mangor; Curwood, Evan K; Vaughan, David N; Omidvarnia, Amir H; Jackson, Graeme D

    2016-04-01

    Individuals with focal epilepsy have heterogeneous sites of seizure origin. However, there may be brain regions that are common to most cases of intractable focal epilepsy. In this study, we aim to identify these using multivariate analysis of task-free functional MRI. Fourteen subjects with extratemporal focal epilepsy and 14 healthy controls were included in the study. Task-free functional MRI data were used to calculate voxel-wise regional connectivity with regional homogeneity (ReHo) and weighted degree centrality (DCw), in addition to regional activity using fraction of amplitude of low-frequency fluctuations (fALFF). Multivariate pattern analysis was applied to each of these metrics to discriminate brain areas that differed between focal epilepsy subjects and healthy controls. ReHo and DCw classified focal epilepsy subjects from healthy controls with high accuracy (89.3% and 75%, respectively). However, fALFF did not significantly classify patients from controls. Increased regional network activity in epilepsy subjects was seen in the ipsilateral piriform cortex, insula, and thalamus, in addition to the dorsal anterior cingulate cortex and lateral frontal cortices. Decreased regional connectivity was observed in the ventromedial prefrontal cortex, as well as lateral temporal cortices. Patients with extratemporal focal epilepsy have common areas of abnormality (ReHo and DCw measures), including the ipsilateral piriform cortex, temporal neocortex, and ventromedial prefrontal cortex. ReHo shows additional increase in the "salience network" that includes anterior insula and anterior cingulate cortex. DCw showed additional effects in the ipsilateral thalamus and striatum. These brain areas may represent key regional network properties underlying focal epilepsy. PMID:26537783

  5. [Exchange reactions in brain tissue under chronic ethanol intoxication].

    PubMed

    Gil'miiarova, F N; Radomskaia, V M; Vinogradova, L N

    1982-01-01

    The paper deals with characterization of systems utilizing ethanol and reactions conjugated with its exchange in the brain tissue under chronic alcohol intoxication. The following is established: the absence of the alcoholdehydrogenase pathway of ethanol oxidation in rabbits, unbalanced splitting of carbohydrates under two-months ethanol load, disturbance of oxidative processes in the tricarboxylic acids cycle, a decrease in the pool of oxidized nicotin amide coenzymes. PMID:7036487

  6. Pharmacological mitigation of tissue damage during brain microdialysis.

    PubMed

    Nesbitt, Kathryn M; Jaquins-Gerstl, Andrea; Skoda, Erin M; Wipf, Peter; Michael, Adrian C

    2013-09-01

    Microdialysis sampling in the brain is employed frequently in the chemical analysis of neurological function and disease, but implanting the probes, which are substantially larger than the size and spacing of brain cells and blood vessels, is injurious and triggers ischemia, gliosis, and cell death at the sampling site. The nature of the interface between the brain and the microdialysis probe is critical to the use of microdialysis as a neurochemical analysis technique. The objective of the work reported here was to investigate the potential of two compounds, dexamethasone, a glucocorticoid anti-inflammatory agent, and XJB-5-131, a mitochondrially targeted reactive oxygen species scavenger, to mitigate the penetration injury. Measurements were performed in the rat brain striatum, which is densely innervated by axons that release dopamine, an electroactive neurotransmitter. We used voltammetry to measure electrically evoked dopamine release next to microdialysis probes during the retrodialysis of dexamethasone or XJB-5-131. After the in vivo measurements, the brain tissue containing the microdialysis probe tracks was examined by fluorescence microscopy using markers for ischemia, neuronal nuclei, macrophages, and dopamine axons and terminals. Dexamethasone and XJB-5-131 each diminished the loss of evoked dopamine activity, diminished ischemia, diminished the loss of neuronal nuclei, diminished the appearance of extravasated macrophages, and diminished the loss of dopamine axons and terminals next to the probes. Our findings confirm the ability of dexamethasone and XJB-5-131 to mitigate, but not eliminate, the effects of the penetration injury caused by implanting microdialysis probes into brain tissue. PMID:23927692

  7. Potassium Channel Complex Autoimmunity Induced by Inhaled Brain Tissue Aerosol

    PubMed Central

    Meeusen, Jeffrey W.; Klein, Christopher J.; Pirko, Istvan; Haselkorn, Keegan E.; Kryzer, Thomas J.; Pittock, Sean J.; Lachance, Daniel H.; Dyck, P. James; Lennon, Vanda A.

    2011-01-01

    Objective Test the hypothesis that autoimmunity induced by inhalation of aerosolized brain tissue caused outbreaks of sensory-predominant polyradiculoneuropathy among swine abattoir employees in Midwestern USA Methods Mice were exposed intranasally, 5 days weekly, to liquefied brain tissue. Serum from exposed mice, patients and unaffected abattoir employees were analyzed for clinically pertinent neural autoantibodies. Results Patients, coworkers and mice exposed to liquefied brain tissue had an autoantibody profile dominated by neural cation channel IgGs. The most compelling link between patients and exposed mice was MRI evidence of grossly swollen spinal nerve roots. Autoantibody responses in patients and mice were dose-dependent and declined after antigen exposure ceased. Autoantibodies detected most frequently, and at high levels, bound to detergent-solubilized macromolecular complexes containing neuronal voltage-gated potassium channels ligated with a high affinity Kv1 channel antagonist, 125I-α-dendrotoxin. Exposed mice exhibited a behavioral phenotype consistent with potassium channel dysfunction recognized in drosophila with mutant (“shaker”) channels: reduced sensitivity to isoflurane-induced anesthesia. Pathological and electrophysiological findings in patients supported peripheral nerve hyperexcitability over destructive axonal loss. The pain-predominant symptoms were consistent with sensory nerve hyperexcitability Interpretation Our observations establish that inhaled neural antigens readily induce neurological autoimmunity and identify voltage-gated potassium channel complexes as a major immunogen. PMID:22451206

  8. In vivo bubble nucleation probability in sheep brain tissue.

    PubMed

    Gateau, J; Aubry, J-F; Chauvet, D; Boch, A-L; Fink, M; Tanter, M

    2011-11-21

    Gas nuclei exist naturally in living bodies. Their activation initiates cavitation activity, and is possible using short ultrasonic excitations of high amplitude. However, little is known about the nuclei population in vivo, and therefore about the rarefaction pressure required to form bubbles in tissue. A novel method dedicated to in vivo investigations was used here that combines passive and active cavitation detection with a multi-element linear ultrasound probe (4-7 MHz). Experiments were performed in vivo on the brain of trepanated sheep. Bubble nucleation was induced using a focused single-element transducer (central frequency 660 kHz, f-number = 1) driven by a high power (up to 5 kW) electric burst of two cycles. Successive passive recording and ultrafast active imaging were shown to allow detection of a single nucleation event in brain tissue in vivo. Experiments carried out on eight sheep allowed statistical studies of the bubble nucleation process. The nucleation probability was evaluated as a function of the peak negative pressure. No nucleation event could be detected with a peak negative pressure weaker than -12.7 MPa, i.e. one order of magnitude higher than the recommendations based on the mechanical index. Below this threshold, bubble nucleation in vivo in brain tissues is a random phenomenon. PMID:22015981

  9. Heparan sulfate deficiency in autistic postmortem brain tissue from the subventricular zone of the lateral ventricles

    PubMed Central

    Pearson, Brandon L.; Corley, Michael J.; Vasconcellos, Amy; Blanchard, D. Caroline; Blanchard, Robert J.

    2013-01-01

    Abnormal cellular growth and organization have been characterized in postmortem tissue from brains of autistic individuals, suggestive of pathology in a critical neurogenic niche, the subventricular zone (SVZ) of the brain lateral ventricles (LV). We examined cellular organization, cell proliferation, and constituents of the extracellular matrix such as N-sulfated heparan sulfate (HS) and laminin (LAM) in postmortem brain tissue from the LV-SVZ of young to elderly individuals with autism (n = 4) and age-matched typically developing (TD) individuals (n = 4) using immunofluorescence techniques. Strong and systematic reductions in HS immunofluorescence were observed in the LV-SVZ of the TD individuals with increasing age. For young through mature, but not elderly, autistic pair members, HS was reduced compared to their matched TDs. Cellular proliferation (Ki67+) was higher in the autistic individual of the youngest age-matched pair. These preliminary data suggesting that HS may be reduced in young to mature autistic individuals are in agreement with previous findings from the BTBR T+tf/J mouse, an animal model of autism; from mice with genetic modifications reducing HS; and with genetic variants in HS-related genes in autism. They suggest that aberrant extracellular matrix glycosaminoglycan function localized to the subventricular zone of the lateral ventricles may be a biomarker for autism, and potentially involved in the etiology of the disorder. PMID:23318464

  10. Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

    ERIC Educational Resources Information Center

    Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

    2012-01-01

    Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

  11. Brain Gray Matter Abnormalities in First-Episode, Treatment-Naive Children with Obsessive-Compulsive Disorder

    PubMed Central

    Cheng, Bochao; Cai, Wu; Wang, Xiuli; Lei, Du; Guo, Yingkun; Yang, Xun; Wu, Qizhu; Gong, Jianping; Gong, Qiyong; Ning, Gang

    2016-01-01

    Although several magnetic resonance imaging (MRI) studies have been conducted in children with obsessive-compulsive disorder (OCD), the brain structural abnormalities in OCD, especially in children, are not yet well characterized. We aimed to identify gray matter (GM) abnormalities in the early stage of pediatric OCD and examine the relationship between these structural abnormalities with clinical characteristics. Examinations of 30 first-episode, treatment-naive pediatric OCD patients without any comorbidities and 30 matched healthy controls (HCs) were performed with 3.0 T magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) was used to conduct voxel-wise tests for group differences in regional gray matter volume (GMV). Compared to HCs, the patient group exhibited more GMV in the bilateral putamen and left orbitofrontal cortex (OFC) and less GMV in the left inferior parietal lobule (IPL). The GMV alternation in the right putamen of OCD patients was positively correlated with Hamilton Anxiety Rating Scale (HAM-A) scores, while the GMV alternation in the left IPL exhibited a trend to negatively correlate with HAM-A scores. Our current results suggest that the GM abnormalities were defined in the early stage of pediatric OCD. Moreover, these findings provided further evidence of brain GM abnormalities that are not only present in the classical fronto–striatal–thalamic circuit but also in the default mode network (DMN), which may represent the interaction of abnormally functional organization of both network in pediatric OCD. PMID:27445736

  12. Brain Gray Matter Abnormalities in First-Episode, Treatment-Naive Children with Obsessive-Compulsive Disorder.

    PubMed

    Cheng, Bochao; Cai, Wu; Wang, Xiuli; Lei, Du; Guo, Yingkun; Yang, Xun; Wu, Qizhu; Gong, Jianping; Gong, Qiyong; Ning, Gang

    2016-01-01

    Although several magnetic resonance imaging (MRI) studies have been conducted in children with obsessive-compulsive disorder (OCD), the brain structural abnormalities in OCD, especially in children, are not yet well characterized. We aimed to identify gray matter (GM) abnormalities in the early stage of pediatric OCD and examine the relationship between these structural abnormalities with clinical characteristics. Examinations of 30 first-episode, treatment-naive pediatric OCD patients without any comorbidities and 30 matched healthy controls (HCs) were performed with 3.0 T magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) following Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) was used to conduct voxel-wise tests for group differences in regional gray matter volume (GMV). Compared to HCs, the patient group exhibited more GMV in the bilateral putamen and left orbitofrontal cortex (OFC) and less GMV in the left inferior parietal lobule (IPL). The GMV alternation in the right putamen of OCD patients was positively correlated with Hamilton Anxiety Rating Scale (HAM-A) scores, while the GMV alternation in the left IPL exhibited a trend to negatively correlate with HAM-A scores. Our current results suggest that the GM abnormalities were defined in the early stage of pediatric OCD. Moreover, these findings provided further evidence of brain GM abnormalities that are not only present in the classical fronto-striatal-thalamic circuit but also in the default mode network (DMN), which may represent the interaction of abnormally functional organization of both network in pediatric OCD. PMID:27445736

  13. Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities

    PubMed Central

    Lyons, W. Ernest; Mamounas, Laura A.; Ricaurte, George A.; Coppola, Vincenzo; Reid, Susan W.; Bora, Susan H.; Wihler, Cornelia; Koliatsos, Vassilis E.; Tessarollo, Lino

    1999-01-01

    Brain-derived neurotrophic factor (BDNF) has trophic effects on serotonergic (5-HT) neurons in the central nervous system. However, the role of endogenous BDNF in the development and function of these neurons has not been established in vivo because of the early postnatal lethality of BDNF null mice. In the present study, we use heterozygous BDNF+/− mice that have a normal life span and show that these animals develop enhanced intermale aggressiveness and hyperphagia accompanied by significant weight gain in early adulthood; these behavioral abnormalities are known to correlate with 5-HT dysfunction. Forebrain 5-HT levels and fiber density in BDNF+/− mice are normal at an early age but undergo premature age-associated decrements. However, young adult BDNF+/− mice show a blunted c-fos induction by the specific serotonin releaser-uptake inhibitor dexfenfluramine and alterations in the expression of several 5-HT receptors in the cortex, hippocampus, and hypothalamus. The heightened aggressiveness can be ameliorated by the selective serotonin reuptake inhibitor fluoxetine. Our results indicate that endogenous BDNF is critical for the normal development and function of central 5-HT neurons and for the elaboration of behaviors that depend on these nerve cells. Therefore, BDNF+/− mice may provide a useful model to study human psychiatric disorders attributed to dysfunction of serotonergic neurons. PMID:10611369

  14. Microscopy and chemical imaging of Behcet brain tissue

    NASA Astrophysics Data System (ADS)

    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.

  15. Brain structural abnormalities in patients with major depression with or without generalized anxiety disorder comorbidity.

    PubMed

    Canu, Elisa; Kostić, Milutin; Agosta, Federica; Munjiza, Ana; Ferraro, Pilar M; Pesic, Danilo; Copetti, Massimiliano; Peljto, Amir; Lecic Tosevski, Dusica; Filippi, Massimo

    2015-05-01

    An overlap frequently occurs between major depression disorder (MDD) and generalized anxiety disorder (GAD). Aim of this study was to assess cortical and white matter (WM) alterations in MDD patients with or without GAD comorbidity. Seventy-one MDD patients and 71 controls were recruited. All subjects underwent T1-weighted and diffusion tensor (DT)/MRI. MRI metrics of cortical thickness and WM integrity were obtained from atlas-based cortical regions and the interhemispheric and major long association WM tracts. Between-group MRI comparisons and multiple regressions with clinical scale scores were performed. Compared to controls, both MDD and MDD-GAD patients showed a cortical thinning of the middle frontal cortex bilaterally, left medial frontal gyrus and frontal pole. Compared to controls and MDD patients, MDD-GAD cases also showed a thinning of the right medial orbitofrontal and fusiform gyri, and left temporal pole and lateral occipital cortices. Compared to controls, MDD patients showed DT MRI abnormalities of the right parahippocampal tract and superior longitudinal fasciculus bilaterally, while no WM alterations were found in MDD-GAD. In all patients, brain abnormalities were related with symptom severity. MDD and MDD-GAD share a common pattern of cortical alterations located in the frontal regions. However, while both the cortex and WM integrity are affected in MDD, only the former is affected in MDD-GAD. These findings support the notion of MDD-GAD as a distinct clinical entity, providing insights into patient vulnerability for specific networks as well as into patient resilience factors reflected by the integrity of other cerebral circuits. PMID:25794861

  16. Raman molecular imaging of brain frozen tissue sections.

    PubMed

    Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

    2014-10-01

    Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins. PMID:25038847

  17. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

    PubMed Central

    2010-01-01

    Background The Rett Syndrome (RTT) brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1) or are involved in synaptic vesicle cycling (dynamin 1). RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP) analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited. PMID:20420693

  18. The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses

    PubMed Central

    2010-01-01

    Background Proton Magnetic Resonance (MR) Spectroscopy (MRS) is a widely available technique for those clinical centres equipped with MR scanners. Unlike the rest of MR-based techniques, MRS yields not images but spectra of metabolites in the tissues. In pathological situations, the MRS profile changes and this has been particularly described for brain tumours. However, radiologists are frequently not familiar to the interpretation of MRS data and for this reason, the usefulness of decision-support systems (DSS) in MRS data analysis has been explored. Results This work presents the INTERPRET DSS version 3.0, analysing the improvements made from its first release in 2002. Version 3.0 is aimed to be a program that 1st, can be easily used with any new case from any MR scanner manufacturer and 2nd, improves the initial analysis capabilities of the first version. The main improvements are an embedded database, user accounts, more diagnostic discrimination capabilities and the possibility to analyse data acquired under additional data acquisition conditions. Other improvements include a customisable graphical user interface (GUI). Most diagnostic problems included have been addressed through a pattern-recognition based approach, in which classifiers based on linear discriminant analysis (LDA) were trained and tested. Conclusions The INTERPRET DSS 3.0 allows radiologists, medical physicists, biochemists or, generally speaking, any person with a minimum knowledge of what an MR spectrum is, to enter their own SV raw data, acquired at 1.5 T, and to analyse them. The system is expected to help in the categorisation of MR Spectra from abnormal brain masses. PMID:21114820

  19. Detection of liver cancer and abnormal liver tissue by Raman spectroscopy and fluorescence

    NASA Astrophysics Data System (ADS)

    Li, Xiaozhou; Ding, Jianhua; Zhang, Xiujun; Lin, Junxiu; Wang, Deli

    2005-01-01

    In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver disease patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5nm is higher than that excited by 488.0nm. For the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. Except for human serum, we use rats serum for researching either. Compared with results of path al examination, we analyze the spectra of normal cases, hepatic fibrosis and hepatocirrhosis respectively in an attempt to find some difference between them. Red shift of fluorescence peak is observed with disease evolution using 514.5nm excitation of an Ar-ion laser. However, no distinct changes happen with 488.0nm excitation. These results have important reference values to explore the method of laser spectrum diagnosis.

  20. The Neural Underpinnings of Associative Learning in Health and Psychosis: How Can Performance Be Preserved When Brain Responses Are Abnormal?

    PubMed Central

    Murray, Graham K.; Corlett, Philip R.; Fletcher, Paul C.

    2010-01-01

    Associative learning experiments in schizophrenia and other psychoses reveal subtle abnormalities in patients’ brain responses. These are sometimes accompanied by intact task performance. An important question arises: How can learning occur if the brain system is not functioning normally? Here, we examine a series of possible explanations for this apparent discrepancy: (1) standard brain activation patterns may be present in psychosis but partially obscured by greater noise, (2) brain signals may be more sensitive to real group differences than behavioral measures, and (3) patients may achieve comparable levels of performance to control subjects by employing alternative or compensatory neural strategies. We consider these explanations in relation to data from causal- and reward-learning imaging experiments in first-episode psychosis patients. The findings suggest that a combination of these factors may resolve the question of why performance is sometimes preserved when brain patterns are disrupted. PMID:20154201

  1. Abnormal Subcortical Brain Morphology in Patients with Knee Osteoarthritis: A Cross-sectional Study

    PubMed Central

    Mao, Cui Ping; Bai, Zhi Lan; Zhang, Xiao Na; Zhang, Qiu Juan; Zhang, Lei

    2016-01-01

    Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA), little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to the healthy control subjects by using high-resolution MRI. Structural MR data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB’s integrated registration and segmentation tool. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004). There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027). Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected) for the caudate nucleus. Hemispheric asymmetry (right larger than left) of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA. PMID:26834629

  2. Sources of abnormal EEG activity in the presence of brain lesions.

    PubMed

    Fernández-Bouzas, A; Harmony, T; Bosch, J; Aubert, E; Fernández, T; Valdés, P; Silva, J; Marosi, E; Martínez-López, M; Casián, G

    1999-04-01

    In routine clinical EEG, a common origin is assumed for delta and theta rhythms produced by brain lesions. In previous papers, we have provided some experimental support, based on High Resolution qEEG and dipole fitting in the frequency domain, for the hypothesis that delta and theta spectral power have independent origins related to lesion and edema respectively. This paper describes the results obtained with Frequency Domain VARETA (FD-VARETA) in a group of 13 patients with cortical space-occupying lesions, in order to: 1) Test the accuracy of FD-VARETA for the localization of brain lesions, and 2) To provide further support for the independent origin of delta and theta components. FD VARETA is a distributed inverse solution, constrained by the Montreal Neurological Institute probabilistic atlas that estimates the spectra of EEG sources. In all patients, logarithmic transformed source spectra were compared with age-matched normative values, defining the Z source spectrum. Maximum Z values were found in 10 patients within the delta band (1.56 to 3.12 Hz); the spatial extent of these sources in the atlas corresponded with the location of the tumors in the CT. In 2 patients with small metastases and large volumes of edema and in a patient showing only edema, maximum Z values were found between 4.29 and 5.12 Hz. The spatial extent of the sources at these frequencies was within the volume of the edema in the CT. These results provided strong support to the hypothesis that both delta and theta abnormal EEG activities are the counterparts of two different pathophysiological processes. PMID:10358783

  3. Protective effects of some creatine derivatives in brain tissue anoxia.

    PubMed

    Perasso, Luisa; Lunardi, Gian Luigi; Risso, Federica; Pohvozcheva, Anna V; Leko, Maria V; Gandolfo, Carlo; Florio, Tullio; Cupello, Aroldo; Burov, Sergey V; Balestrino, Maurizio

    2008-05-01

    Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia. PMID:17940889

  4. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

    PubMed

    van Erp, T G M; Hibar, D P; Rasmussen, J M; Glahn, D C; Pearlson, G D; Andreassen, O A; Agartz, I; Westlye, L T; Haukvik, U K; Dale, A M; Melle, I; Hartberg, C B; Gruber, O; Kraemer, B; Zilles, D; Donohoe, G; Kelly, S; McDonald, C; Morris, D W; Cannon, D M; Corvin, A; Machielsen, M W J; Koenders, L; de Haan, L; Veltman, D J; Satterthwaite, T D; Wolf, D H; Gur, R C; Gur, R E; Potkin, S G; Mathalon, D H; Mueller, B A; Preda, A; Macciardi, F; Ehrlich, S; Walton, E; Hass, J; Calhoun, V D; Bockholt, H J; Sponheim, S R; Shoemaker, J M; van Haren, N E M; Hulshoff Pol, H E; Pol, H E H; Ophoff, R A; Kahn, R S; Roiz-Santiañez, R; Crespo-Facorro, B; Wang, L; Alpert, K I; Jönsson, E G; Dimitrova, R; Bois, C; Whalley, H C; McIntosh, A M; Lawrie, S M; Hashimoto, R; Thompson, P M; Turner, J A

    2016-04-01

    The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness. PMID:26033243

  5. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  6. Brain tissue tessellation shows absence of canonical microcircuits.

    PubMed

    Peters, James F; Tozzi, Arturo; Ramanna, Sheela

    2016-07-28

    We provide a novel, fast and cheap method for the morphological evaluation of simple 2-D images taken from histological samples. This method, based on computational geometry, leads to a novel kind of "tessellation" of every type of biological picture, in order to locate the zones equipped with very fine-grained differences in the tissue texture, compared with the surrounding ones. As an example, we apply the technique to the evaluation of histological images from brain sections and demonstrate that the cortical layers, rather than being a canonical assembly of homogeneous cells as usually believed, display scattered neuronal micro-clusters equipped with higher activity than the surrounding ones. PMID:27222926

  7. Seizure control with thermal energy? Modeling of heat diffusivity in brain tissue and computer-based design of a prototype mini-cooler.

    SciTech Connect

    Osario, I.; Chang, F.-C.; Gopalsami, N.; Nuclear Engineering Division; Univ. of Kansas

    2009-10-01

    Automated seizure blockage is a top priority in epileptology. Lowering nervous tissue temperature below a certain level suppresses abnormal neuronal activity, an approach with certain advantages over electrical stimulation, the preferred investigational therapy for pharmacoresistant seizures. A computer model was developed to identify an efficient probe design and parameters that would allow cooling of brain tissue by no less than 21 C in 30 s, maximum. The Pennes equation and the computer code ABAQUS were used to investigate the spatiotemporal behavior of heat diffusivity in brain tissue. Arrays of distributed probes deliver sufficient thermal energy to decrease, inhomogeneously, brain tissue temperature from 37 to 20 C in 30 s and from 37 to 15 C in 60 s. Tissue disruption/loss caused by insertion of this probe is considerably less than that caused by ablative surgery. This model may be applied for the design and development of cooling devices for seizure control.

  8. Novel Cell and Tissue Acquisition System (CTAS): Microdissection of Live and Frozen Brain Tissues

    PubMed Central

    Kudo, Lili C.; Vi, Nancy; Ma, Zhongcai; Fields, Tony; Avliyakulov, Nuraly K.; Haykinson, Michael J.; Bragin, Anatol; Karsten, Stanislav L.

    2012-01-01

    We developed a novel, highly accurate, capillary based vacuum-assisted microdissection device CTAS - Cell and Tissue Acquisition System, for efficient isolation of enriched cell populations from live and freshly frozen tissues, which can be successfully used in a variety of molecular studies, including genomics and proteomics. Specific diameter of the disposable capillary unit (DCU) and precisely regulated short vacuum impulse ensure collection of the desired tissue regions and even individual cells. We demonstrated that CTAS is capable of dissecting specific regions of live and frozen mouse and rat brain tissues at the cellular resolution with high accuracy. CTAS based microdissection avoids potentially harmful physical treatment of tissues such as chemical treatment, laser irradiation, excessive heat or mechanical cell damage, thus preserving primary functions and activities of the dissected cells and tissues. High quality DNA, RNA, and protein can be isolated from CTAS-dissected samples, which are suitable for sequencing, microarray, 2D gel-based proteomic analyses, and Western blotting. We also demonstrated that CTAS can be used to isolate cells from native living tissues for subsequent recultivation of primary cultures without affecting cellular viability, making it a simple and cost-effective alternative for laser-assisted microdissection. PMID:22855692

  9. Experimental studies with selected light sources for NIRS of brain tissue: quantifying tissue chromophore concentration

    NASA Astrophysics Data System (ADS)

    Myllylä, Teemu; Korhonen, Vesa; Kiviniemi, Vesa; Tuchin, Valery

    2015-03-01

    Near-infrared spectroscopy (NIRS) based techniques are utilised in quantifying changes of chromophore concentrations in tissue. Particularly, non-invasive in vivo measurements of tissue oxygenation in the cerebral cortex are of interest. The measurement method is based on illuminating tissue and measuring the back-scattered light at wavelengths of interest. Tissue illumination can be realised using different techniques and various light sources. Commonly, lasers and laser diodes (LD) are utilised, but also high-power light emitting diodes (HPLED) are becoming more common. At the moment, a wide range of available narrow-band light sources exists, covering basically the entire spectrum of interest in brain tissue NIRS measurements. In this paper, in the centre of our interest are LDs and HPLEDs, because of their affordability, efficiency in terms of radiant flux versus size and easiness to adopt in in vivo medical applications. We compare characteristics of LDs and HPLEDs at specific wavelengths and their suitability for in vivo quantifying of different tissue chromophore concentration, particularly in cerebral blood flow (CBF). A special focus is on shape and width of the wavelength bands of interest, generated by the LDs and HPLEDs. Moreover, we experimentally study such effects as, spectroscopy cross talk, separability and signal-to-noise ratio (SNR) when quantifying tissue chromophore concentration. Chromophores of our interest are cytochrome, haemoglobin and water. Various LDs and HPLEDs, producing narrow-band wavelengths in the range from 500 nm to 1000 nm are tested.

  10. Analysis of potassium dynamics in mammalian brain tissue.

    PubMed Central

    Gardner-Medwin, A R

    1983-01-01

    Equations are derived for potassium (K+) dynamics in simplified models of brain tissue. These describe K+ movement in extracellular space, transfer of K+ associated with current flow through cells (the so-called spatial buffer mechanism) and equilibration between extracellular space and cytoplasm. Numerical calculations show that the principal data on K+ dynamics from various laboratories can be accounted for with simple assumptions about spatial buffer action and uptake. Much of the data is inconsistent with extracellular diffusion being the main mechanism for K+ flux through brain tissue, including some that has earlier been cited in support of this hypothesis. The buffering actions of spatial buffer transfer of K+ and of cytoplasmic equilibration, in which these mechanisms reduce rises of [K+]o that would otherwise occur, are analysed quantitatively for specific K+ source distributions and for spatial and temporal frequency components of general disturbances. Spatial buffer action has most effect in reducing [K+]o rises with net release over extensive zones of tissue (greater than ca. 200 micron in diameter) for periods of the order of minutes. Reductions greater than 75% may be achieved. With localized but prolonged release, the maximum [K+]o rise is little affected but the volume of tissue affected by more moderate rises is substantially reduced. Cytoplasmic K+ uptake also has most effect with widespread release, but its effect diminishes with prolonged periods of release. The effects of the buffering mechanisms and of K+ re-uptake into active neurones in determining the decline of [K+]o after a period of stimulation are considered. Re-uptake is unlikely to be the major factor responsible for [K+]o decline when this has a time course of only a few seconds. The properties necessary for the cells mediating the spatial buffer mechanisms, possibly glial cells, are assessed. PMID:6875885

  11. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  12. The duplication 17p13.3 phenotype: analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes.

    PubMed

    Curry, Cynthia J; Rosenfeld, Jill A; Grant, Erica; Gripp, Karen W; Anderson, Carol; Aylsworth, Arthur S; Saad, Taha Ben; Chizhikov, Victor V; Dybose, Giedre; Fagerberg, Christina; Falco, Michelle; Fels, Christina; Fichera, Marco; Graakjaer, Jesper; Greco, Donatella; Hair, Jennifer; Hopkins, Elizabeth; Huggins, Marlene; Ladda, Roger; Li, Chumei; Moeschler, John; Nowaczyk, Malgorzata J M; Ozmore, Jillian R; Reitano, Santina; Romano, Corrado; Roos, Laura; Schnur, Rhonda E; Sell, Susan; Suwannarat, Pim; Svaneby, Dea; Szybowska, Marta; Tarnopolsky, Mark; Tervo, Raymond; Tsai, Anne Chun-Hui; Tucker, Megan; Vallee, Stephanie; Wheeler, Ferrin C; Zand, Dina J; Barkovich, A James; Aradhya, Swaroop; Shaffer, Lisa G; Dobyns, William B

    2013-08-01

    Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well-known Miller-Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34 additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter- and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large duplications that include both the YWHAE and LIS1 genes. These patients had a relatively distinct facial phenotype and frequent structural brain abnormalities involving the corpus callosum, cerebellar vermis, and cranial base. Autism spectrum disorders were seen in a third of duplication probands, most commonly in those with duplications of YWHAE and flanking genes such as CRK. The typical neurobehavioral phenotype was usually seen in those with the larger duplications. We did not confirm the association of early overgrowth with involvement of YWHAE and CRK, or growth failure with duplications of LIS1. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt ABR, while the SHFLD phenotype was associated with duplication of BHLHA9 as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome. PMID:23813913

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

    PubMed Central

    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 < 0.001) suggests that lutein has a role in neural development. The relationship remained significant but weaker in older adults (r = 0.51, P < 0.05) and insignificant in centenarians (r = 0.08, 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. PMID:27205891

  14. Comparative Tissue Stainability of Lawsonia inermis (Henna) and Eosin as Counterstains to Hematoxylin in Brain Tissues.

    PubMed

    Alawa, Judith N; Gideon, Gbenga O; Adetiba, Bamidele; Alawa, Clement B

    2015-04-01

    We hyposthesized that henna staining could provide an alternative to eosin when used as a counterstain to hematoxylin for understanding basic neurohistological principles. Therefore, this study was aimed at investigating the suitability of henna as counterstain to hematoxylin for the demonstration of the layer stratification and cellular distribution in the brain tissue. Henna stained nervous tissue by reacting with the basic elements in proteins via its amino groups. It stained the neuropil and connective tissue membranes brown and effectively outlined the perikarya of neurons with no visible nuclei demonstrating that it is an acidic dye. Henna as a counterstain to hematoxylin demonstrated reliability as a new neurohistological stain. It facilitated identification of cortical layer stratification and cellular distribution in brain tissue sections from Wistar rats. This was comparable to standard hematoxylin and eosin staining as morphological and morphometrical analyses of stained cells did not show significant differences in size or number. This study presents a method for staining with henna and demonstrates that although henna and eosin belong to different dye groups (anthraquinone and xanthenes, respectively) based on their chromophores, they share similar staining techniques and thus could be used interchangeably in neurohistology. PMID:25772039

  15. Cardiolipin and electron transport chain abnormalities in mouse brain tumor mitochondria: lipidomic evidence supporting the Warburg theory of cancer*

    PubMed Central

    Kiebish, Michael A.; Han, Xianlin; Cheng, Hua; Chuang, Jeffrey H.; Seyfried, Thomas N.

    2008-01-01

    Otto Warburg first proposed that cancer originated from irreversible injury to mitochondrial respiration, but the structural basis for this injury has remained elusive. Cardiolipin (CL) is a complex phospholipid found almost exclusively in the inner mitochondrial membrane and is intimately involved in maintaining mitochondrial functionality and membrane integrity. Abnormalities in CL can impair mitochondrial function and bioenergetics. We used shotgun lipidomics to analyze CL content and composition in highly purified brain mitochondria from the C57BL/6J (B6) and VM/Dk (VM) inbred strains and from subcutaneously grown brain tumors derived from these strains to include an astrocytoma and ependymoblastoma (B6 tumors), a stem cell tumor, and two microgliomas (VM tumors). Major abnormalities in CL content or composition were found in all tumors. The compositional abnormalities involved an abundance of immature molecular species and deficiencies of mature molecular species, suggesting major defects in CL synthesis and remodeling. The tumor CL abnormalities were also associated with significant reductions in both individual and linked electron transport chain activities. A mathematical model was developed to facilitate data interpretation. The implications of our findings to the Warburg cancer theory are discussed. PMID:18703489

  16. Increases in brain white matter abnormalities and subcortical gray matter are linked to CD4 recovery in HIV infection.

    PubMed

    Fennema-Notestine, Christine; Ellis, Ronald J; Archibald, Sarah L; Jernigan, Terry L; Letendre, Scott L; Notestine, Randy J; Taylor, Michael J; Theilmann, Rebecca J; Julaton, Michelle D; Croteau, David J; Wolfson, Tanya; Heaton, Robert K; Gamst, Anthony C; Franklin, Donald R; Clifford, David B; Collier, Ann C; Gelman, Benjamin B; Marra, Christina; McArthur, Justin C; McCutchan, J Allen; Morgello, Susan; Simpson, David M; Grant, Igor

    2013-08-01

    MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79 % initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis. PMID:23838849

  17. Abnormal structure of the canine oncogene, related to the human c-yes-1 oncogene, in canine mammary tumor tissue.

    PubMed

    Miyoshi, N; Tateyama, S; Ogawa, K; Yamaguchi, R; Kuroda, H; Yasuda, N; Shimizu, T

    1991-12-01

    Cellular oncogenes of genomic DNA in 6 canine primary mammary tumors were screened by Southern blot analysis, using 7 oncogene probes. A canine genomic oncogene related to the human c-yes-1 oncogene was detected as abnormal bands in solid carcinoma genomic DNA digested with EcoRI, HindIII, HindIII-EcoRI, or HindIII-BamHI. Comparison was made between other tumor specimens and control specimens obtained from 4 clinically normal dogs--1 mixed breed and 3 Shiba Inu dogs (the same breed as the dog from which the solid carcinoma was obtained). These abnormal bands were 0.1 to 1 kilobase shorter than the normal gene. However, digestion of genomic DNA obtained from normal WBC of this dog also produced all of the abnormal bands as observed in digested DNA from the solid carcinoma tissue. Therefore, in this dog, the genomic DNA of all somatic cells from the ontogenic stage still had the abnormal sequences related to the human c-yes-1 oncogene, and it is possible that this abnormal structure may have some role (eg, as an initiator) in tumorigenesis or the progression of this tumor. PMID:1789521

  18. Brain tissue slice thickness monitored by ion-profile measurement.

    PubMed

    Lipinski, H G

    1992-04-01

    The thickness of a brain tissue slice preparation governs the amount of time required for substances to diffuse from the bathing solution to preparation. Slice thickness may increase during the experiment, e.g., in cases of hypoxia where osmotic pressure within the tissue changes, enabling water to enter the preparation. With increasing slice thickness diffusion paths from the bath to central layers of the preparation increase possibly resulting in an insufficient O2 supply to central layers. Therefore, the actual slice thickness should be monitored during the experiment especially in cases where osmolarity is changed or during hypoxia. This paper describes a simple method to monitor the actual slice thickness using ion profiles measured by ion selective micro-electrodes driven at a constant rate of approximately 10 microns/s (sample rate ca. 10/s). The method is based on steep changes in the concentration gradients at the upper and lower surfaces of the preparation induced by simple diffusion in the presence of concentration gradients between the non-tortuous bath and the tortuous tissue. The thickness of the preparation is derived from the location of the steep gradient changes as reflected by the registered profile. PMID:1405733

  19. Magnetic resonance brain tissue segmentation based on sparse representations

    NASA Astrophysics Data System (ADS)

    Rueda, Andrea

    2015-12-01

    Segmentation or delineation of specific organs and structures in medical images is an important task in the clinical diagnosis and treatment, since it allows to characterize pathologies through imaging measures (biomarkers). In brain imaging, segmentation of main tissues or specific structures is challenging, due to the anatomic variability and complexity, and the presence of image artifacts (noise, intensity inhomogeneities, partial volume effect). In this paper, an automatic segmentation strategy is proposed, based on sparse representations and coupled dictionaries. Image intensity patterns are singly related to tissue labels at the level of small patches, gathering this information in coupled intensity/segmentation dictionaries. This dictionaries are used within a sparse representation framework to find the projection of a new intensity image onto the intensity dictionary, and the same projection can be used with the segmentation dictionary to estimate the corresponding segmentation. Preliminary results obtained with two publicly available datasets suggest that the proposal is capable of estimating adequate segmentations for gray matter (GM) and white matter (WM) tissues, with an average overlapping of 0:79 for GM and 0:71 for WM (with respect to original segmentations).

  20. Experimental and numerical study on the mechanical behavior of rat brain tissue.

    PubMed

    Karimi, A; Navidbakhsh, M; Yousefi, H; Haghi, A Motevalli; Sadati, Sja

    2014-02-01

    Brain tissue is a very soft tissue in which the mechanical properties depend on the loading direction. While few studies have characterized these biomechanical properties, it is worth knowing that accurate characterization of the mechanical properties of brain tissue at different loading directions is a key asset for neuronavigation and surgery simulation through haptic devices. In this study, the hyperelastic mechanical properties of rat brain tissue were measured experimentally and computationally. Prepared cylindrical samples were excised from the parietal lobes of rats' brains and experimentally tested by a tensile testing machine. The effects of loading direction on the mechanical properties of brain tissue were measured by applying load on both longitudinal and circumferential directions. The general prediction ability of the proposed hyperelastic model was verified using finite element (FE) simulations of brain tissue tension experiments. The uniaxial experimental results compared well with those predicted by the FE models. The results revealed the influence of loading direction on the mechanical properties of brain tissue. The Ogden hyperelastic material model was suitably represented by the non-linear behavior of the brain tissue, which can be used in future biomechanical simulations. The hyperelastic properties of brain tissue provided here have interest to the medical research community as there are several applications where accurate characterization of these properties are crucial for an accurate outcome, such as neurosurgery, robotic surgery, haptic device design or car manufacturing to evaluate possible trauma due to an impact. PMID:24519528

  1. Microwave irradiation of human brain tissue: production of microscopic slides within one day.

    PubMed Central

    Boon, M E; Marani, E; Adriolo, P J; Steffelaar, J W; Bots, G T; Kok, L P

    1988-01-01

    A three step method using microwave irradiation enabled microscopic slides of human brain tissue to be obtained within one working day: steps 1 and 2 hardened and solidified brain tissue; step 3 completed formalin fixation. The efficacy and precision of the method was compared with slides of conventionally processed brain tissue that had been fixed in formalin for six weeks. The microscopic quality of the sections was excellent with good presentation of brain tissue and equalled that of conventionally processed slides. Images Fig 1 Fig 2 Fig 3 PMID:3290268

  2. 5-hydroxymethylcytosine is detected in RNA from mouse brain tissues.

    PubMed

    Miao, Zhigang; Xin, Ning; Wei, Bin; Hua, Xiaodong; Zhang, Gaocai; Leng, Cuihua; Zhao, Chenyu; Wu, Di; Li, Jizhen; Ge, Wei; Sun, Miao; Xu, Xingshun

    2016-07-01

    5-hydroxymethylcytosine (5hmC) is considered as a novel DNA modification and plays an important role in cancer, stem cells, and developmental diseases. In this study, we demonstrated the existence of RNA 5hmC modification in mouse brain RNA by using a dot blot analysis method. Our data indicated that 5hmC modification in RNA samples was less than that in DNA samples. Further, we optimized the conditions for 5hmC detection in RNA samples such as DNase treatment, denature reagents, denature time, sample air-dry time, and the cross-linking time between RNA and membrane. Our results demonstrated that DNase treatment and denature reagents were two important factors that affected the 5hmC detection in RNA samples. By using the optimal conditions for RNA 5hmC detection, we found that the brainstem, the hippocampus, and the cerebellum had high levels of 5hmC modification and 5mC modification in RNA. Finally, we found that RNA 5hmC modification decreased in MPTP-induced Parkinson's disease model in mice. These suggest that 5hmC modification in RNA might play an important regulative role on protein or microRNA expression in these brain tissues. Because DNA 5hmC modification plays an important role in neural differentiation and development as well as neurological diseases, the significance of 5hmC modification in RNA in different neurological diseases needs further investigation. In summary, our study demonstrated for the first time the abundance of 5hmC modification in brain RNA by using a dot blot analysis method and proved that dot blot analysis is a useful method for 5hmC detection in RNA samples. PMID:27117867

  3. Optical changes of porcine brain tissue after thermal coagulation

    NASA Astrophysics Data System (ADS)

    Schwarzmaier, Hans-Joachim; Goldbach, Thomas; Yaroslavsky, Ilya V.; Ulrich, Frank; Bettag, Martin; Kahn, Thomas; Kaufmann, Raimund

    1995-05-01

    Porcine brain tissue is a model for human brain structures in laser induced thermo-therapy. However, its optical properties including possible heat-related changes were basically unknown so far. To simulate laser coagulation, 12 specimens (6 grey and 6 white matter) were heated in a saline bath (80°C, 2 hours) and compared to 11 untreated samples (5 grey and 6 white matter). The optical constants were obtained from transmission (total and collimated) and reflection (diffuse) measurements using the inverse Monte-Carlo method. The absorption coefficient ((mu) a) of untreated grey substance decreased from 0.35 +/- 0.06/mm (340 nm) to 0.03 +/- 0.02/mm (800 nm). The scattering coefficient ((mu) s) varied between 20.42 +/- 3.65/mm (340 nm) and 6.85 +/- 2.07/mm (800 nm). The anisotropy factor (g) increased from 0.848 +/- 0.013 (340 nm) to 0.889 +/- 0.009 (800 nm). Coagulation increased (mu) a up to a factor of 2 (340-540 nm; p < 0.05), and (mu) s by a factor up to 3 (340-800 nm, all data p < 0.001) while g was decreased up to 18% (340-560 nm; p < 0.05). White substance exhibited a (mu) a between 0.24 +/- 0.07/mm (340 nm) and 0.04 +/- 0.02/mm (800 nm) while (mu) s varied between 26.72 +/- 9.10/mm (340 nm) and 21.78 +/- 3.88/mm (800 nm). The g-value increased from 0.561 +/- 0.180 (340 nm) to 0.834 +/- 0.068 (800 nm). Coagulation increased (mu) a by a factor up to 2 (340-800 nm; all data p < 0.05) while (mu) s and g remained unchanged. Thermal denaturation changes the absorption and scattering properties of porcine brain significantly.

  4. Annual Research Review: Growth connectomics – the organization and reorganization of brain networks during normal and abnormal development

    PubMed Central

    Vértes, Petra E; Bullmore, Edward T

    2015-01-01

    Background We first give a brief introduction to graph theoretical analysis and its application to the study of brain network topology or connectomics. Within this framework, we review the existing empirical data on developmental changes in brain network organization across a range of experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans). Synthesis We discuss preliminary evidence and current hypotheses for how the emergence of network properties correlates with concomitant cognitive and behavioural changes associated with development. We highlight some of the technical and conceptual challenges to be addressed by future developments in this rapidly moving field. Given the parallels previously discovered between neural systems across species and over a range of spatial scales, we also review some recent advances in developmental network studies at the cellular scale. We highlight the opportunities presented by such studies and how they may complement neuroimaging in advancing our understanding of brain development. Finally, we note that many brain and mind disorders are thought to be neurodevelopmental in origin and that charting the trajectory of brain network changes associated with healthy development also sets the stage for understanding abnormal network development. Conclusions We therefore briefly review the clinical relevance of network metrics as potential diagnostic markers and some recent efforts in computational modelling of brain networks which might contribute to a more mechanistic understanding of neurodevelopmental disorders in future. PMID:25441756

  5. Circulating Omega‐3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study

    PubMed Central

    Virtanen, Jyrki K.; Siscovick, David S.; Lemaitre, Rozenn N.; Longstreth, William T.; Spiegelman, Donna; Rimm, Eric B.; King, Irena B.; Mozaffarian, Dariush

    2013-01-01

    Background Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results In the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake. Conclusions Among older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation. PMID:24113325

  6. MEASUREMENT OF SMALL MECHANICAL VIBRATIONS OF BRAIN TISSUE EXPOSED TO EXTREMELY-LOW-FREQUENCY ELECTRIC FIELDS

    EPA Science Inventory

    Electromagnetic fields can interact with biological tissue both electrically and mechanically. This study investigated the mechanical interaction between brain tissue and an extremely-low-frequency (ELF) electric field by measuring the resultant vibrational amplitude. The exposur...

  7. Microwave dielectric measurements and tissue characteristics of the human brain: potential in localizing intracranial tissues

    NASA Astrophysics Data System (ADS)

    Axer, Hubertus; Gräßel, David; Steinhauer, Matthias; Stöhr, Peter; John, Andreas; Coenen, Volker A.; Jansen, Rolf H.; Keyserlingk, Diedrich Graf v.

    2002-05-01

    This study describes the measurements of dielectric properties in the microwave range to differentiate various human central nervous structures. Using a vector network analyser transmission and reflection coefficients were measured from 500 MHz to 18 GHz in four human formalin fixed human brains. The positions of the electrodes were marked, and the tissue was histologically stained to visualize the myelo- and the cytoarchitecture as well as the nerve fibre orientation at the electrodes. The profiles of the transmission coefficients showed a characteristic minimum peak. In order to describe this peak, a mathematical function was fitted. Parameters derived from digital image processing were used to characterize the myelo- and cytoarchitecure of the tissue at the electrodes. A multiple regression model, with the frequency at the transmission peak minimum as a dependent variable and two tissue characteristics at the two electrodes as independent variables, showed a multiple regression coefficient of 0.765. A neural network model was able to estimate the frequency at the transmission peak minimum from the tissue characteristics at the electrode. The measurements of dielectric properties are well suited to differentiate distinct intracerebral structures. The method could be used for online monitoring of the needle's position during a stereotactic intervention in neurosurgery.

  8. Specific binding of naloxone to ovine brain tissue: comparison of brain regions and endocrine states.

    PubMed

    Weesner, G D; Trout, W E; Malven, P V

    1989-06-01

    Binding of [3H]naloxone ([3H]NAL) to brain membranes was quantified by Scatchard analysis using two methods of separating bound from free [3H]NAL. In the centrifugation method, membranes that were soluble at 1,000 x g, but sedimented at 20,000 x g, were incubated with [3H]NAL. For filtration, all membranes that sedimented at 20,000 x g were incubated and filtered through glass filter fibers. Nonspecific binding was estimated using greater than 500-fold excess of unlabeled naloxone (10(-6) M). Specific binding of [3H]NAL was used to generate linear multiple-point Scatchard plots, which indicated a single class of high-affinity sites. In Exp. 1, 10 ovariectomized (OVX) ewes were injected with estradiol-17 beta alone or in combination with progesterone. Compared with OVX controls, these hormonal treatments did not affect binding of [3H]NAL (centrifugation method) to combined hypothalamus (HYP) + preoptic (POA) tissues. In cyclic ewes (Exp. 2, filtration method), affinity constants (2.4 +/- .2 x 10(8) M-1) did not differ among HYP, POA and basal forebrain (BF) tissues, but BF had more sites (39 +/- 3 fmol/mg) than either HYP (14 +/- 1) or POA (17 +/- 1). Binding affinity and concentration of sites within each brain area (HYP, POA, BF) did not differ between d 8 and d 16 (preovulatory but after luteolysis) in normally cycling ewes. Overall, neural tissue dissected from BF had a greater concentration of binding sites than HYP or POA. Exogenous and endogenous fluctuations in ovarian steroids did not affect binding of [3H]NAL to these tissues. PMID:2768110

  9. Building Biocompatible Hydrogels for Tissue Engineering of the Brain and Spinal Cord

    PubMed Central

    Aurand, Emily R.; Wagner, Jennifer; Lanning, Craig; Bjugstad, Kimberly B.

    2012-01-01

    Tissue engineering strategies employing biomaterials have made great progress in the last few decades. However, the tissues of the brain and spinal cord pose unique challenges due to a separate immune system and their nature as soft tissue. Because of this, neural tissue engineering for the brain and spinal cord may require re-establishing biocompatibility and functionality of biomaterials that have previously been successful for tissue engineering in the body. The goal of this review is to briefly describe the distinctive properties of the central nervous system, specifically the neuroimmune response, and to describe the factors which contribute to building polymer hydrogels compatible with this tissue. These factors include polymer chemistry, polymerization and degradation, and the physical and mechanical properties of the hydrogel. By understanding the necessities in making hydrogels biocompatible with tissue of the brain and spinal cord, tissue engineers can then functionalize these materials for repairing and replacing tissue in the central nervous system. PMID:24955749

  10. Regional brain abnormalities in 22q11.2 deletion syndrome: association with cognitive abilities and behavioral symptoms.

    PubMed

    Bearden, Carrie E; van Erp, Theo G M; Monterosso, John R; Simon, Tony J; Glahn, David C; Saleh, Peter A; Hill, Nicole M; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Cannon, Tyrone D

    2004-06-01

    Children with 22q11.2 microdeletions (Velocardiofacial Syndrome; VCFS) have previously been shown to exhibit learning deficits and elevated rates of psychopathology. The aim of this study was to assess regional brain abnormalities in children with 22q11DS, and to determine the relationship of these measures to neurocognitive and behavioral function. Thirteen children with confirmed deletions and 9 demographically matched comparison subjects were assessed with a neurocognitive battery, behavioral measures, and high-resolution MRI. Twenty-two qllDS children showed a nonsignificant 4.3% global decrease in total brain volume as compared to healthy controls,with differential reduction in white matter, and significantly increased sulcal cerebrospinal fluid (CSF) in temporal and posterior brain regions. In 22q11 DS subjects, but not controls, bilateral temporal gray and white matter volumes were significant predictors of overall cognitive performance. Further, reduced temporal gray matter was associated with elevated Thought Problems score on the CBCL. Results indicate that global alterations in brain volume are common in children with 22q deletions, particularly those with low IQ and/or behavioral disturbance. Although preliminary,these findings suggest a possible underlying pathophysiology of the cognitive deficits seen in this syndrome,and provide insight into complex gene-brain-behavior relationships. PMID:15788257

  11. An a contrario approach for the detection of patient-specific brain perfusion abnormalities with arterial spin labelling.

    PubMed

    Maumet, Camille; Maurel, Pierre; Ferré, Jean-Christophe; Barillot, Christian

    2016-07-01

    In this paper, we introduce a new locally multivariate procedure to quantitatively extract voxel-wise patterns of abnormal perfusion in individual patients. This a contrario approach uses a multivariate metric from the computer vision community that is suitable to detect abnormalities even in the presence of closeby hypo- and hyper-perfusions. This method takes into account local information without applying Gaussian smoothing to the data. Furthermore, to improve on the standard a contrario approach, which assumes white noise, we introduce an updated a contrario approach that takes into account the spatial coherency of the noise in the probability estimation. Validation is undertaken on a dataset of 25 patients diagnosed with brain tumours and 61 healthy volunteers. We show how the a contrario approach outperforms the massively univariate general linear model usually employed for this type of analysis. PMID:27039702

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

    PubMed

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

    2015-11-01

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

  13. A Cross-Sectional Study of Regional Brain Volume Abnormalities in Lesch-Nyhan Disease and its Variants

    PubMed Central

    Schretlen, David J.; Varvaris, Mark; Ho, Tiffany E.; Vannorsdall, Tracy D.; Gordon, Barry; Harris, James C.; Jinnah, H. A.

    2014-01-01

    Background Lesch-Nyhan disease (LND) is a rare, X-linked, neurodevelopmental metabolic disorder that results from a near-complete lack of hypoxanthine phosphoribosyl-transferase enzyme activity. LND is characterized by hyperuricemia, motor neurological abnormalities, recurrent self-injury, and cognitive impairment, but its neural substrates remain poorly understood. Methods In this cross-sectional study, we measured gray matter abnormalities in 21 persons with LND, 17 with an attenuated variant of the phenotype (LNV), and 33 healthy controls using voxel-based morphometry. We conducted an analysis of covariance to identify group differences in regional gray matter volume (GMV), followed by six pair-wise post-hoc group comparisons. Findings Patients with LND showed 20% smaller intracranial volumes (17% gray and 26% white matter) than healthy adults. The largest differences were found in basal ganglia, frontotemporal, and limbic regions, with sparing of parieto-occipital regions. The gray matter volumes of LNV participants invariably fell between those of patients with classical LND and healthy controls. Compared to healthy adults, patients with LND showed additional GMV reductions in the temporal lobe and left lateralized structures, and patients with LNV showed additional reductions in lingual and precuneus regions with sparing of right frontal and temporal regions. LND participants showed reductions in the ventral striatum and prefrontal areas relative to LNV. Interpretation This study of brain morphology reveals regional abnormalities associated with known neurological and behavioral deficits in persons with LND. It also revealed that patients with LNV show milder gray matter abnormalities in many of the same brain regions and preservation of GMV in other regions which could provide important clues to the neural substrates of differences between thephenotypes. PMID:24383089

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

    NASA Astrophysics Data System (ADS)

    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.

  15. Dyslexic brain activation abnormalities in deep and shallow orthographies: A meta-analysis of 28 functional neuroimaging studies.

    PubMed

    Martin, Anna; Kronbichler, Martin; Richlan, Fabio

    2016-07-01

    We used coordinate-based meta-analysis to objectively quantify commonalities and differences of dyslexic functional brain abnormalities between alphabetic languages differing in orthographic depth. Specifically, we compared foci of under- and overactivation in dyslexic readers relative to nonimpaired readers reported in 14 studies in deep orthographies (DO: English) and in 14 studies in shallow orthographies (SO: Dutch, German, Italian, Swedish). The separate meta-analyses of the two sets of studies showed universal reading-related dyslexic underactivation in the left occipitotemporal cortex (including the visual word form area (VWFA)). The direct statistical comparison revealed higher convergence of underactivation for DO compared with SO in bilateral inferior parietal regions, but this abnormality disappeared when foci resulting from stronger dyslexic task-negative activation (i.e., deactivation relative to baseline) were excluded. Higher convergence of underactivation for DO compared with SO was further identified in the left inferior frontal gyrus (IFG) pars triangularis, left precuneus, and right superior temporal gyrus, together with higher convergence of overactivation in the left anterior insula. Higher convergence of underactivation for SO compared with DO was found in the left fusiform gyrus, left temporoparietal cortex, left IFG pars orbitalis, and left frontal operculum, together with higher convergence of overactivation in the left precentral gyrus. Taken together, the findings support the notion of a biological unity of dyslexia, with additional orthography-specific abnormalities and presumably different compensatory mechanisms. The results are discussed in relation to current functional neuroanatomical models of developmental dyslexia. Hum Brain Mapp 37:2676-2699, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27061464

  16. High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

    PubMed Central

    Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

    2010-01-01

    Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

  17. In vivo multiphoton microscopy of deep brain tissue.

    PubMed

    Levene, Michael J; Dombeck, Daniel A; Kasischke, Karl A; Molloy, Raymond P; Webb, Watt W

    2004-04-01

    Although fluorescence microscopy has proven to be one of the most powerful tools in biology, its application to the intact animal has been limited to imaging several hundred micrometers below the surface. The rest of the animal has eluded investigation at the microscopic level without excising tissue or performing extensive surgery. However, the ability to image with subcellular resolution in the intact animal enables a contextual setting that may be critical for understanding proper function. Clinical applications such as disease diagnosis and optical biopsy may benefit from minimally invasive in vivo approaches. Gradient index (GRIN) lenses with needle-like dimensions can transfer high-quality images many centimeters from the object plane. Here, we show that multiphoton microscopy through GRIN lenses enables minimally invasive, subcellular resolution several millimeters in the anesthetized, intact animal, and we present in vivo images of cortical layer V and hippocampus in the anesthetized Thy1-YFP line H mouse. Microangiographies from deep capillaries and blood vessels containing fluorescein-dextran and quantum dot-labeled serum in wild-type mouse brain are also demonstrated. PMID:14668300

  18. Experimental research of mechanical behavior of porcine brain tissue under rotational shear stress.

    PubMed

    Li, Gang; Zhang, Jianhua; Wang, Kan; Wang, Mingyu; Gao, Changqing; Ma, Chao

    2016-04-01

    The objective of this paper is to investigate mechanical behavior of porcine brain tissue with a series of rotational shear stress control experiments. To this end, several experiments including stress sweep tests, frequency sweep tests and quasi-static creep tests were designed and conducted with a standard rheometer (HAAKE RheoStress6000). The effects of the loading stress rates to mechanical properties of brain tissue were also studied in stress sweep tests. The results of stress sweep tests performed on the same brain showed that brain tissue had an obvious regional inhomogeneity and the mechanical damage occurred at the rotational shear stress of 10-15Pa. The experimental data from three different loading stress rates demonstrated that the mechanical behavior of porcine brain tissue was loading stress rate dependent. With the decrease of loading stress rate, a stiffer mechanical characteristic of brain tissue was observed and the occurrence of mechanical damage can be delayed to a higher stress. From the results of frequency sweep tests we found that brain tissue had almost completely elastic properties at high frequency area. The nonlinear creep response under the rotational shear stress of 1, 3, 5, 7 and 9Pa was shown in results of creep tests. A new nonlinear viscoelastic solid model was proposed for creep tests and matched well with the test data. Considering the regional differences, loading stress rates and test conditions effects, loss tangent tan δ in porcine brain tissue showed a high uniformity of 0.25-0.45. PMID:26735181

  19. Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

    PubMed Central

    Martínez-Montes, Eduardo

    2013-01-01

    This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

  20. Brain MRI abnormalities in the adult form of myotonic dystrophy type 1: A longitudinal case series study.

    PubMed

    Conforti, Renata; de Cristofaro, Mario; Cristofano, Adriana; Brogna, Barbara; Sardaro, Angela; Tedeschi, Gioacchino; Cirillo, Sossio; Di Costanzo, Alfonso

    2016-02-01

    This study aimed to verify whether brain abnormalities, previously described in patients with myotonic dystrophy type 1 (DM1) by magnetic resonance imaging (MRI), progressed over time and, if so, to characterize their progression. Thirteen DM1 patients, who had at least two MRI examinations, were retrospectively evaluated and included in the study. The mean duration (± standard deviation) of follow-up was 13.4 (±3.8) years, over a range of 7-20 years. White matter lesions (WMLs) were rated by semi-quantitative method, the signal intensity of white matter poster-superior to trigones (WMPST) by reference to standard images and brain atrophy by ventricular/brain ratio (VBR). At the end of MRI follow-up, the scores relative to lobar, temporal and periventricular WMLs, to WMPST signal intensity and to VBR were significantly increased compared to baseline, and MRI changes were more evident in some families than in others. No correlation was found between the MRI changes and age, onset, disease duration, muscular involvement, CTG repetition and follow-up duration. These results demonstrated that white matter involvement and brain atrophy were progressive in DM1 and suggested that progression rate varied from patient to patient, regardless of age, disease duration and genetic defect. PMID:26755488

  1. Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study

    PubMed Central

    Han, Lv; Zhaohui, Liu; Fei, Yan; Ting, Li; Pengfei, Zhao; Wang, Du; Cheng, Dong; Pengde, Guo; Xiaoyi, Han; Xiao, Wang; Rui, Li; Zhenchang, Wang

    2014-01-01

    Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients. PMID:24872895

  2. Motor Network Plasticity and Low-Frequency Oscillations Abnormalities in Patients with Brain Gliomas: A Functional MRI Study

    PubMed Central

    Niu, Chen; Zhang, Ming; Min, Zhigang; Rana, Netra; Zhang, Qiuli; Liu, Xin; Li, Min; Lin, Pan

    2014-01-01

    Brain plasticity is often associated with the process of slow-growing tumor formation, which remodels neural organization and optimizes brain network function. In this study, we aimed to investigate whether motor function plasticity would display deficits in patients with slow-growing brain tumors located in or near motor areas, but who were without motor neurological deficits. We used resting-state functional magnetic resonance imaging to probe motor networks in 15 patients with histopathologically confirmed brain gliomas and 15 age-matched healthy controls. All subjects performed a motor task to help identify individual motor activity in the bilateral primary motor cortex (PMC) and supplementary motor area (SMA). Frequency-based analysis at three different frequencies was then used to investigate possible alterations in the power spectral density (PSD) of low-frequency oscillations. For each group, the average PSD was determined for each brain region and a nonparametric test was performed to determine the difference in power between the two groups. Significantly reduced inter-hemispheric functional connectivity between the left and right PMC was observed in patients compared with controls (P<0.05). We also found significantly decreased PSD in patients compared to that in controls, in all three frequency bands (low: 0.01–0.02 Hz; middle: 0.02–0.06 Hz; and high: 0.06–0.1 Hz), at three key motor regions. These findings suggest that in asymptomatic patients with brain tumors located in eloquent regions, inter-hemispheric connection may be more vulnerable. A comparison of the two approaches indicated that power spectral analysis is more sensitive than functional connectivity analysis for identifying the neurological abnormalities underlying motor function plasticity induced by slow-growing tumors. PMID:24806463

  3. Normal and abnormal tissue identification system and method for medical images such as digital mammograms

    NASA Technical Reports Server (NTRS)

    Heine, John J. (Inventor); Clarke, Laurence P. (Inventor); Deans, Stanley R. (Inventor); Stauduhar, Richard Paul (Inventor); Cullers, David Kent (Inventor)

    2001-01-01

    A system and method for analyzing a medical image to determine whether an abnormality is present, for example, in digital mammograms, includes the application of a wavelet expansion to a raw image to obtain subspace images of varying resolution. At least one subspace image is selected that has a resolution commensurate with a desired predetermined detection resolution range. A functional form of a probability distribution function is determined for each selected subspace image, and an optimal statistical normal image region test is determined for each selected subspace image. A threshold level for the probability distribution function is established from the optimal statistical normal image region test for each selected subspace image. A region size comprising at least one sector is defined, and an output image is created that includes a combination of all regions for each selected subspace image. Each region has a first value when the region intensity level is above the threshold and a second value when the region intensity level is below the threshold. This permits the localization of a potential abnormality within the image.

  4. Deletion in the N-terminal Half of Olfactomedin 1 Modifies Its Interaction with Synaptic Proteins and Causes Brain Dystrophy and Abnormal Behavior in Mice

    PubMed Central

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P.; Tomarev, Stanislav I.

    2013-01-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, Teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca2+ concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

  5. Deletion in the N-terminal half of olfactomedin 1 modifies its interaction with synaptic proteins and causes brain dystrophy and abnormal behavior in mice.

    PubMed

    Nakaya, Naoki; Sultana, Afia; Munasinghe, Jeeva; Cheng, Aiwu; Mattson, Mark P; Tomarev, Stanislav I

    2013-12-01

    Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part of the protein, increased neonatal death and reduced body weight of surviving homozygous mice. Magnetic resonance imaging analyses revealed reduced brain volume and attenuated size of white matter tracts such as the anterior commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice demonstrated abnormal behavior in several tests including reduced marble digging, elevated plus maze test, nesting activity and latency on balance beam tests as compared with their wild-type littermates. The olfactory system was both structurally and functionally disturbed by the mutation in the Olfm1 gene as shown by functional magnetic resonance imaging analysis and a smell test. Deficiencies of the olfactory system may contribute to the neonatal death and loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate proteins that co-precipitated with wild-type or mutant Olfm1 proteins in postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, teneurin-4 and Kidins220. Modified interaction of Olfm1 with binding targets led to an increase in intracellular Ca(2+) concentration and activation of ERK1/2, MEK1 and CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated intracellular calcium may contribute to the abnormal behavior and olfactory activity of Olfm1 mutant mice. PMID:24095980

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Abnormal neurological exam findings in individuals with mild traumatic brain injury (mTBI) versus psychiatric and healthy controls.

    PubMed

    Silva, Marc A; Donnell, Alison J; Kim, Michelle S; Vanderploeg, Rodney D

    2012-01-01

    In those with a history of mild traumatic brain injury (mTBI), cognitive and emotional disturbances are often misattributed to that preexisting injury. However, causal determinations of current symptoms cannot be conclusively determined because symptoms are often nonspecific to etiology and offer virtually no differential diagnostic value in postacute or chronic phases. This population-based study examined whether the presence of abnormalities during neurological examination would distinguish between mTBI (in the chronic phase), healthy controls, and selected psychiatric conditions. Retrospective analysis of data from 4462 community-dwelling Army veterans was conducted. Diagnostically unique groups were compared on examination of cranial nerve function and other neurological signs. Results demonstrated that individuals with mTBI were no more likely than those with a major depressive disorder, generalized anxiety disorder, posttraumatic stress disorder, or somatoform disorder to show any abnormality. Thus, like self-reported cognitive and emotional symptoms, the presence of cranial nerve or other neurological abnormalities offers no differential diagnostic value. Clinical implications and study limitations are presented. PMID:23020281

  8. Comparison of nine tractography algorithms for detecting abnormal structural brain networks in Alzheimer’s disease

    PubMed Central

    Zhan, Liang; Zhou, Jiayu; Wang, Yalin; Jin, Yan; Jahanshad, Neda; Prasad, Gautam; Nir, Talia M.; Leonardo, Cassandra D.; Ye, Jieping; Thompson, Paul M.; for the Alzheimer’s Disease Neuroimaging Initiative

    2015-01-01

    Alzheimer’s disease (AD) involves a gradual breakdown of brain connectivity, and network analyses offer a promising new approach to track and understand disease progression. Even so, our ability to detect degenerative changes in brain networks depends on the methods used. Here we compared several tractography and feature extraction methods to see which ones gave best diagnostic classification for 202 people with AD, mild cognitive impairment or normal cognition, scanned with 41-gradient diffusion-weighted magnetic resonance imaging as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. We computed brain networks based on whole brain tractography with nine different methods – four of them tensor-based deterministic (FACT, RK2, SL, and TL), two orientation distribution function (ODF)-based deterministic (FACT, RK2), two ODF-based probabilistic approaches (Hough and PICo), and one “ball-and-stick” approach (Probtrackx). Brain networks derived from different tractography algorithms did not differ in terms of classification performance on ADNI, but performing principal components analysis on networks helped classification in some cases. Small differences may still be detectable in a truly vast cohort, but these experiments help assess the relative advantages of different tractography algorithms, and different post-processing choices, when used for classification. PMID:25926791

  9. Abnormal EEG Complexity and Functional Connectivity of Brain in Patients with Acute Thalamic Ischemic Stroke

    PubMed Central

    Liu, Shuang; Guo, Jie; Meng, Jiayuan; Wang, Zhijun; Yao, Yang; Yang, Jiajia; Qi, Hongzhi; Ming, Dong

    2016-01-01

    Ischemic thalamus stroke has become a serious cardiovascular and cerebral disease in recent years. To date the existing researches mostly concentrated on the power spectral density (PSD) in several frequency bands. In this paper, we investigated the nonlinear features of EEG and brain functional connectivity in patients with acute thalamic ischemic stroke and healthy subjects. Electroencephalography (EEG) in resting condition with eyes closed was recorded for 12 stroke patients and 11 healthy subjects as control group. Lempel-Ziv complexity (LZC), Sample Entropy (SampEn), and brain network using partial directed coherence (PDC) were calculated for feature extraction. Results showed that patients had increased mean LZC and SampEn than the controls, which implied the stroke group has higher EEG complexity. For the brain network, the stroke group displayed a trend of weaker cortical connectivity, which suggests a functional impairment of information transmission in cortical connections in stroke patients. These findings suggest that nonlinear analysis and brain network could provide essential information for better understanding the brain dysfunction in the stroke and assisting monitoring or prognostication of stroke evolution. PMID:27403202

  10. Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

    PubMed Central

    Chen, Lizhou; Huang, Xiaoqi; Lei, Du; He, Ning; Hu, Xinyu; Chen, Ying; Li, Yuanyuan; Zhou, Jinbo; Guo, Lanting; Kemp, Graham J.; Gong, Qiyong

    2015-01-01

    Background Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions. Methods We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups. Results Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD. Limitations This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small. Conclusion Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD. PMID:25853285

  11. Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence.

    PubMed

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

    2005-06-01

    Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage. PMID:15893157

  12. Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

    PubMed Central

    Chen, Jiann-Hwa; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

    2015-01-01

    Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM) and the control rats were separated using two-dimensional gel electrophoresis (2-DE) to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT) and cathepsin D (CATD), which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2) protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia-reperfusion-related neuronal injury

  13. 3D PATTERN OF BRAIN ABNORMALITIES IN WILLIAMS SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

    PubMed Central

    Chiang, Ming-Chang; Reiss, Allan L.; Lee, Agatha D.; Bellugi, Ursula; Galaburda, Albert M.; Korenberg, Julie R.; Mills, Debra L.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with deletion of ~20 contiguous genes in chromosome band 7q11.23. Individuals with WS exhibit mild to moderate mental retardation, but are relatively more proficient in specific language and musical abilities. We used tensor-based morphometry (TBM) to visualize the complex pattern of gray/white matter reductions in WS, based on fluid registration of structural brain images. Methods 3D T1-weighted brain MRIs of 41 WS subjects (age: 29.2±9.2SD years; 23F/18M) and 39 age-matched healthy controls (age: 27.5±7.4 years; 23F/16M) were fluidly registered to a minimum deformation target. Fine-scale volumetric differences were mapped between diagnostic groups. Local regions were identified where regional structure volumes were associated with diagnosis, and with intelligence quotient (IQ) scores. Brain asymmetry was also mapped and compared between diagnostic groups. Results WS subjects exhibited widely distributed brain volume reductions (~10–15% reduction; P < 0.0002, permutation test). After adjusting for total brain volume, the frontal lobes, anterior cingulate, superior temporal gyrus, amygdala, fusiform gyrus and cerebellum were found to be relatively preserved in WS, but parietal and occipital lobes, thalamus and basal ganglia, and midbrain were disproportionally decreased in volume (P < 0.0002). These regional volumes also correlated positively with performance IQ in adult WS subjects (age ≥ 30 years, P = 0.038). Conclusion TBM facilitates 3D visualization of brain volume reductions in WS. Reduced parietal/occipital volumes may be associated with visuospatial deficits in WS. By contrast, frontal lobes, amygdala, and cingulate gyrus are relatively preserved or even enlarged, consistent with unusual affect regulation and language production in WS. PMID:17512756

  14. Predictors of Abnormal Neuroimaging of the Brain in Children With Epilepsy Aged 1 Month to 2 Years: Useful Clues in a Resource-Limited Setting.

    PubMed

    Sanmaneechai, Oranee; Danchaivijitr, Nasuda; Likasitwattanakul, Surachai

    2015-10-01

    Neuroimaging should be performed on infants with seizure. However, there are economic limitations in performing neuroimaging in a resource-limited setting. The younger the age, the higher the risk of having abnormal neuroimaging. The aim was to determine frequency and predictors of abnormal neuroimaging in children with epilepsy aged 1 month to 2 years. History, physical examination, electroencephalogram (EEG), and neuroimaging were reviewed. Thirty-seven of 49 (76%) had neuroimaging studies; 19 computed tomography (CT), 14 magnetic resonance imaging (MRI), and 4 had both. Abnormal neuroimaging was found in 19 (51%). Predictors of abnormal neuroimages are developmental delay, abnormal head circumference, and abnormal neurologic examination. Eight children (21%) had lesions on neuroimaging studies that altered or influenced management. Of 8 patients with normal examination and EEG, 1 had a brain tumor and another had arteriovenous malformation. Neuroimaging should be considered as an essential aid in the evaluation of infants with epilepsy, even in a resource-limited setting. PMID:25792429

  15. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    PubMed

    Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. PMID:26497829

  16. Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

    2016-01-01

    The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

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

    PubMed

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

    2015-11-01

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

  18. Diagnostic yield and accuracy of postmortem cytological sampling from the brain surface of animals with neurological abnormalities.

    PubMed

    Wünsche, S; Rosati, M; Matiasek, K

    2016-05-01

    Clarification of central nervous system (CNS) disorders frequently requires pathological investigation via brain biopsy or postmortem examination. The use of cytology is usually restricted to diagnosis of mass lesions and septic meningitis. The value of brain cytology at postmortem examination has not been explored sufficiently. This study aimed to clarify the diagnostic value of meningeal imprint cytology at postmortem brain examination. Samples were taken from cerebrum and cerebellum and stained with the modified Wright stain and with haematoxylin-eosin. The slides were evaluated and findings were compared to brain histopathology with respect to resemblance, discrepancy and diagnostic validity. The study included 169 cases involving multiple animal species. Histopathology identified inflammatory disorders in 60/135 (44.4%) cases, neoplasia in 19/135 (14.1%) and non-infiltrative diseases in 56/135 (41.5%). Cytology revealed pathological changes in 79/135 (58.5%) of these cases. The histopathological diagnosis was reproduced in 57/135 (42.2%) cases, 43/57 (75.4%) of which were inflammatory. Non-diagnostic cases included 16/135 (11.9%) with sub-diagnostic cytological features and 3/135 (2.2%) with unclear phenomena. In 55/135 (40.7%) of brains with histological lesions, cytology proved inferior, providing negative results, including 40/55 (72.7%) cases with non-infiltrative diseases, 12/55 (21.8%) with inflammation and 3/55 (5.5%) with neoplasia. Conversely, 3/34 (8.8%) of controls showed cytological abnormalities. Cytological sampling from CNS adds to the sensitivity of neuropathological investigations, even if restricted to non-invasive surface imprints. The diagnostic accuracy exceeds 40%, with infiltrative diseases being five times more likely to be detected than non-infiltrative diseases. PMID:27009475

  19. Irradiation-injured brain tissues can self-renew in the absence of the pivotal tumor suppressor p53 in the medaka (Oryzias latipes) embryo

    PubMed Central

    Yasuda, Takako; Kimori, Yoshitaka; Nagata, Kento; Igarashi, Kento; Watanabe-Asaka, Tomomi; Oda, Shoji; Mitani, Hiroshi

    2016-01-01

    The tumor suppressor protein, p53, plays pivotal roles in regulating apoptosis and proliferation in the embryonic and adult central nervous system (CNS) following neuronal injuries such as those induced by ionizing radiation. There is increasing evidence that p53 negatively regulates the self-renewal of neural stem cells in the adult murine brain; however, it is still unknown whether p53 is essential for self-renewal in the injured developing CNS. Previously, we demonstrated that the numbers of apoptotic cells in medaka (Oryzias latipes) embryos decreased in the absence of p53 at 12–24 h after irradiation with 10-Gy gamma rays. Here, we used histology to examine the later morphological development of the irradiated medaka brain. In p53-deficient larvae, the embryonic brain possessed similar vacuoles in the brain and retina, although the vacuoles were much smaller and fewer than those found in wild-type embryos. At the time of hatching (6 days after irradiation), no brain abnormality was observed. In contrast, severe disorganized neuronal arrangements were still present in the brain of irradiated wild-type embryos. Our present results demonstrated that self-renewal of the brain tissue completed faster in the absence of p53 than wild type at the time of hatching because p53 reduces the acute severe neural apoptosis induced by irradiation, suggesting that p53 is not essential for tissue self-renewal in developing brain. PMID:26410759

  20. Air Pollution, Cognitive Deficits and Brain Abnormalities: A Pilot Study with Children and Dogs

    ERIC Educational Resources Information Center

    Calderon-Garciduenas, Lilian; Mora-Tiscareno, Antonieta; Ontiveros, Esperanza; Gomez-Garza, Gilberto; Barragan-Mejia, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R.; Henriquez-Roldan, Carlos; Perez-Guille, Beatriz; Torres-Jardon, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E.; Gonzalez-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C.; Engle, Randall W.

    2008-01-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n:55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic…

  1. Co-Localisation of Abnormal Brain Structure and Function in Specific Language Impairment

    ERIC Educational Resources Information Center

    Badcock, Nicholas A.; Bishop, Dorothy V. M.; Hardiman, Mervyn J.; Barry, Johanna G.; Watkins, Kate E.

    2012-01-01

    We assessed the relationship between brain structure and function in 10 individuals with specific language impairment (SLI), compared to six unaffected siblings, and 16 unrelated control participants with typical language. Voxel-based morphometry indicated that grey matter in the SLI group, relative to controls, was increased in the left inferior…

  2. Abnormal Functional MRI BOLD Contrast in the Vegetative State after Severe Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Heelmann, Volker

    2010-01-01

    For the rehabilitation process, the treatment of patients surviving brain injury in a vegetative state is still a serious challenge. The aim of this study was to investigate patients exhibiting severely disturbed consciousness using functional magnetic resonance imaging. Five cases of posttraumatic vegetative state and one with minimal…

  3. Tobacco Smoking and MRI/MRS Brain Abnormalities Compared to Nonsmokers

    PubMed Central

    Domino, E.F.

    2008-01-01

    This mini review emphasizes the fact that tobacco smoking causes small but real biologic brain changes that need to be studied in depth. A crucial question is whether these anatomical/chemical changes reverse toward normal when smokers quit. This review is presented to stimulate further research to answer this question. PMID:18817837

  4. Brief Report: Abnormal Association between the Thalamus and Brain Size in Asperger's Disorder

    ERIC Educational Resources Information Center

    Hardan, Antonio Y.; Girgis, Ragy R.; Adams, Jason; Gilbert, Andrew R.; Melhem, Nadine M.; Keshavan, Matcheri S.; Minshew, Nancy J.

    2008-01-01

    The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation…

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

    NASA Astrophysics Data System (ADS)

    Emin, David; Akhtari, Massoud; Ellingson, B. M.; Mathern, G. W.

    2015-08-01

    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.

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

    SciTech Connect

    Emin, David; Akhtari, Massoud; Ellingson, B. M.; Mathern, G. W.

    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.

  7. Adolescent Binge Drinking Linked to Abnormal Spatial Working Memory Brain Activation: Differential Gender Effects

    PubMed Central

    Squeglia, Lindsay M.; Schweinsburg, Alecia Dager; Pulido, Carmen; Tapert, Susan F.

    2011-01-01

    Background Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. Methods 40 binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males) ages 16 to 19, completed neuropsychological testing, substance use interviews, and a spatial working memory task (SWM) during functional magnetic resonance imaging (fMRI). Results Significant binge drinking status x gender interactions were found (p<.05) in 8 brain regions spanning bilateral frontal, anterior cingulate, temporal, and cerebellar cortices. In all regions, female binge drinkers showed less SWM activation than female controls, while male bingers exhibited greater SWM response than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances (ps<.025). For male binge drinkers, greater activation was linked to better spatial performance (p<.025). Conclusion Binge drinking during adolescence is associated with gender-specific differences in frontal, temporal, and cerebellar brain activation during a SWM task, which in turn relate to cognitive performance. Activation correlates with neuropsychological performance, strengthening the argument that BOLD activation is both affected by alcohol use and is an important indicator of behavioral functioning. Females may be more vulnerable to the neurotoxic effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive

  8. Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Kim, Sun-Young; Choi, Uk-Su; Park, Sung-Yeon; Oh, Se-Hong; Yoon, Hyo-Woon; Koh, Yun-Joo; Im, Woo-Young; Park, Jee-In; Song, Dong-Ho

    2015-01-01

    Objective The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC). Methods Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC. Results When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation. Conclusion These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion. PMID:25670944

  9. Brain metabolite concentrations are associated with illness severity scores and white matter abnormalities in very preterm infants

    PubMed Central

    Card, Dallas; Nossin-Manor, Revital; Moore, Aideen M.; Raybaud, Charles; Sled, John G.; Taylor, Margot J.

    2016-01-01

    Background Magnetic resonance spectroscopy allows for the noninvasive study of brain metabolism and therefore may provide useful information about brain injuries. We examined the associations of brain metabolite ratios in very preterm infants with white matter lesions and overall health status at birth. Methods Spectroscopy data were obtained from 99 very preterm infants (born ≤32wk gestation) imaged shortly after birth and from 67 of these infants at term-equivalent age. These data were processed using LC Model. Multiple regression was used to examine the association of metabolite ratios with focal non cystic white matter lesions visible on conventional magnetic resonance imaging (MRI) and with at-birth illness severity scores. Results Within 2wk of birth, the ratio of N-acetylaspartate + N-acetylaspartylglutamate to creatine + phosphocreatine was significantly lower in those infants showing white matter abnormalities on conventional MRI. Increased lactate to creatine + phosphocreatine and lactate to glycerophosphocholine + phosphocholine ratios were significantly associated with increasing severity of Clinical Risk Index for Babies II and Apgar scores taken at 1 and 5min after birth. Conclusion Both overall health status at birth and white matter injury in preterm neonates are reflected in metabolite ratios measured shortly after birth. Long-term follow-up will provide additional insight into the prognostic value of these measures. PMID:23575877

  10. Structural and functional brain abnormalities place phenocopy frontotemporal dementia (FTD) in the FTD spectrum

    PubMed Central

    Steketee, Rebecca M.E.; Meijboom, Rozanna; Bron, Esther E.; Osse, Robert Jan; de Koning, Inge; Jiskoot, Lize C.; Klein, Stefan; de Jong, Frank Jan; van der Lugt, Aad; van Swieten, John C.; Smits, Marion

    2016-01-01

    Purpose ‘Phenocopy’ frontotemporal dementia (phFTD) patients may clinically mimic the behavioral variant of FTD (bvFTD), but do not show functional decline or abnormalities upon visual inspection of routine neuroimaging. We aimed to identify abnormalities in gray matter (GM) volume and perfusion in phFTD and to assess whether phFTD belongs to the FTD spectrum. We compared phFTD patients with both healthy controls and bvFTD patients. Materials & methods Seven phFTD and 11 bvFTD patients, and 20 age-matched controls underwent structural T1-weighted magnetic resonance imaging (MRI) and 3D pseudo-continuous arterial spin labeling (pCASL) at 3T. Normalized GM (nGM) volumes and perfusion, corrected for partial volume effects, were quantified regionally as well as in the entire supratentorial cortex, and compared between groups taking into account potential confounding effects of gender and scanner. Results PhFTD patients showed cortical atrophy, most prominently in the right temporal lobe. Apart from this regional atrophy, GM volume was generally not different from either controls or from bvFTD. BvFTD however showed extensive frontotemporal atrophy. Perfusion was increased in the left prefrontal cortex compared to bvFTD and to a lesser extent to controls. Conclusion PhFTD and bvFTD show overlapping cortical structural abnormalities indicating a continuum of changes especially in the frontotemporal regions. Together with functional changes suggestive of a compensatory response to incipient pathology in the left prefrontal regions, these findings are the first to support a possible neuropathological etiology of phFTD and suggest that phFTD may be a neurodegenerative disease on the FTD spectrum. PMID:27222795

  11. Mitochondrial DNA Rearrangement Spectrum in Brain Tissue of Alzheimer’s Disease: Analysis of 13 Cases

    PubMed Central

    Chen, Yucai; Liu, Changsheng; Parker, William Davis; Chen, Hongyi; Beach, Thomas G.; Liu, Xinhua; Serrano, Geidy E.; Lu, Yanfen; Huang, Jianjun; Yang, Kunfang; Wang, Chunmei

    2016-01-01

    Background Mitochondrial dysfunction may play a central role in the pathologic process of Alzheimer’s disease (AD), but there is still a scarcity of data that directly links the pathology of AD with the alteration of mitochondrial DNA. This study aimed to provide a comprehensive assessment of mtDNA rearrangement events in AD brain tissue. Patients and Methods Postmortem frozen human brain cerebral cortex samples were obtained from the Banner Sun Health Research Institute Brain and Body Donation Program, Sun City, AZ. Mitochondria were isolated and direct sequence by using MiSeq®, and analyzed by relative software. Results Three types of mitochondrial DNA (mtDNA) rearrangements have been seen in post mortem human brain tissue from patients with AD and age matched control. These observed rearrangements include a deletion, F-type rearrangement, and R-type rearrangement. We detected a high level of mtDNA rearrangement in brain tissue from cognitively normal subjects, as well as the patients with Alzheimer's disease (AD). The rate of rearrangements was calculated by dividing the number of positive rearrangements by the coverage depth. The rearrangement rate was significantly higher in AD brain tissue than in control brain tissue (17.9%versus 6.7%; p = 0.0052). Of specific types of rearrangement, deletions were markedly increased in AD (9.2% versus 2.3%; p = 0.0005). Conclusions Our data showed that failure of mitochondrial DNA in AD brain might be important etiology of AD pathology. PMID:27299301

  12. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  13. Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain

    PubMed Central

    Herbst, Eric AF; Holloway, Graham P

    2015-01-01

    Abstract Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia–reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. PMID:25529987

  14. Soya protein ameliorates the metabolic abnormalities of dysfunctional adipose tissue of dyslipidaemic rats fed a sucrose-rich diet.

    PubMed

    Oliva, María E; Selenscig, Dante; D'Alessandro, María E; Chicco, Adriana; Lombardo, Yolanda B

    2011-04-01

    The present study investigates whether the replacement of dietary casein by soya protein isolate could be able to improve and/or even revert the morphological and metabolic abnormalities underlying the adipose tissue dysfunction of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). For this purpose, Wistar rats were fed a SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed a SRD in which the source of protein, casein, was substituted by soya. The control group received a diet in which the source of carbohydrate was maize starch. Compared with the SRD-fed group, the results showed that: (1) soya protein decreased body-weight gain, limited the accretion of visceral adiposity and decreased adipose tissue cell volume without changes in total cell number; (2) soya protein increased the protein mass expression of PPARγ, which was significantly reduced in the fat pad of the SRD-fed rats; (3) the activity of the enzymes involved in the de novo lipogenesis of adipose tissue was significantly decreased/normalised; (4) soya protein corrected the inhibitory effect of SRD upon the anti-lipolytic action of insulin, reduced basal lipolysis and normalised the protein mass expression of GLUT-4. Dyslipidaemia, glucose homeostasis and plasma leptin levels returned to control values. The present study provides data showing the beneficial effects of soya protein to improve and/or revert the adipose tissue dysfunction of a dyslipidaemic insulin-resistant rat model and suggests that soya could maintain the functionality of the adipose tissue-liver axis improving/reverting lipotoxicity. PMID:21118606

  15. Plasticity of Nonneuronal Brain Tissue: Roles in Developmental Disorders

    ERIC Educational Resources Information Center

    Dong, Willie K.; Greenough, William T.

    2004-01-01

    Neuronal and nonneuronal plasticity are both affected by environmental and experiential factors. Remodeling of existing neurons induced by such factors has been observed throughout the brain, and includes alterations in dendritic field dimensions, synaptogenesis, and synaptic morphology. The brain loci affected by these plastic neuronal changes…

  16. Brain gene expression differences are associated with abnormal tail biting behavior in pigs.

    PubMed

    Brunberg, E; Jensen, P; Isaksson, A; Keeling, L J

    2013-03-01

    Knowledge about gene expression in animals involved in abnormal behaviors can contribute to the understanding of underlying biological mechanisms. This study aimed to explore the motivational background to tail biting, an abnormal injurious behavior and severe welfare problem in pig production. Affymetrix microarrays were used to investigate gene expression differences in the hypothalamus and prefrontal cortex of pigs performing tail biting, pigs receiving bites to the tail and neutral pigs who were not involved in the behavior. In the hypothalamus, 32 transcripts were differentially expressed (P < 0.05) when tail biters were compared with neutral pigs, 130 when comparing receiver pigs with neutrals, and two when tail biters were compared with receivers. In the prefrontal cortex, seven transcripts were differently expressed in tail biters when compared with neutrals, seven in receivers vs. neutrals and none in the tail biters vs. receivers. In total, 19 genes showed a different expression pattern in neutral pigs when compared with both performers and receivers. This implies that the functions of these may provide knowledge about why the neutral pigs are not involved in tail biting behavior as performers or receivers. Among these 19 transcripts were genes associated with production traits in pigs (PDK4), sociality in humans and mice (GTF2I) and novelty seeking in humans (EGF). These are in line with hypotheses linking tail biting with reduced back fat thickness and explorative behavior. PMID:23146156

  17. Abnormal Cortical Development after Premature Birth Shown by Altered Allometric Scaling of Brain Growth

    PubMed Central

    Kapellou, Olga; Counsell, Serena J; Kennea, Nigel; Dyet, Leigh; Saeed, Nadeem; Stark, Jaroslav; Maalouf, Elia; Duggan, Philip; Ajayi-Obe, Morenike; Hajnal, Jo; Allsop, Joanna M; Boardman, James; Rutherford, Mary A; Cowan, Frances; Edwards, A. David

    2006-01-01

    Background We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment. Methods and Findings We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25–1.33), which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001) independent of intrauterine or postnatal somatic growth. Conclusions Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery. PMID:16866579

  18. Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder.

    PubMed

    Pang, Elizabeth W; Valica, Tatiana; MacDonald, Matt J; Taylor, Margot J; Brian, Jessica; Lerch, Jason P; Anagnostou, Evdokia

    2016-02-01

    A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high-functioning autism (mean age: 11.43 years) and 21 age- and sex-matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. PMID:26363154

  19. Cross-sectional and longitudinal abnormalities in brain structure in children with severe mood dysregulation or bipolar disorder

    PubMed Central

    Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

    2012-01-01

    Background There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in bipolar disorder (BD) have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time. Furthermore, the developmental trajectories of structural abnormalities in BD or SMD are unknown. This study provides such data in BD, SMD, and HV. Methods An optimized, modulated voxel-based morphometry (VBM) analysis was conducted on structural MRI scans from 201 children (78 SMD, 55 BD, and 68 HV). Additionally, 92 children (31 SMD, 34 BD, and 27 HV) were re-scanned after two years (mean interval 1.99 ± 0.94 years), to compare time-related changes among the three groups. Results Cross-sectionally, the groups differed in gray matter (GM) volume in pre-supplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), insula, and globus pallidus. The cortical differences were driven mainly by increased GM volume in HV compared to BD and SMD. In globus pallidus, there was increased GM in BD compared to HV and SMD. Longitudinally, group-by-time interactions were evident in two clusters in the superior/inferior parietal lobule (R SPL/IPL) and in the precuneus. In both clusters, the interactions were driven by an abnormal increase in volume in BD. Conclusions Cross-sectionally, both BD and SMD are associated with structural abnormalities in frontal cortex, insula, and basal ganglia. While some of these deficits overlap (insula and DLPFC), others differentiate SMD and BD (pre-SMA and globus pallidus). Abnormal developmental trajectories in lateral parietal cortex and precuneus are present in, and unique to, BD. Because of the high proportion of co-occurring ADHD in the SMD subjects, we could not separate effects of ADHD from those of SMD, and future research including a non-irritable ADHD group must

  20. Differential Impact of Hyponatremia and Hepatic Encephalopathy on Health-Related Quality of Life and Brain Metabolite Abnormalities in Cirrhosis

    PubMed Central

    Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, HoChong; Heuman, Douglas M; Bajaj, Jasmohan S

    2013-01-01

    Background Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality-of-life (HRQOL) and cognition in cirrhosis. Aim To study effect of hyponatremia on cognition, HRQOL and brain MR spectroscopy (MRS) independent of HE. Methods Four cirrhotic groups(no HE/HN, HE alone, HN alone (sodium<130mEq/L),HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psycho-social and physical sub-scores) and brain MRS (myoinositol(mI) and glutamate+glutamine(Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. Results 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN and 10 HN, MELD 12, 63% Hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN:3, HN:3.5, HE:6.5,HE+HN:7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP(p<0.0001, all comparisons). Brain MRS showed lowest Glx in HN and highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE,HE+HN and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psycho-social SIP scores. Conclusions Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. PMID:23665182

  1. Comparison of positron emission tomography, cognition, and brain volume in Alzheimer's disease with and without severe abnormalities of white matter.

    PubMed Central

    DeCarli, C; Grady, C L; Clark, C M; Katz, D A; Brady, D R; Murphy, D G; Haxby, J V; Salerno, J A; Gillette, J A; Gonzalez-Aviles, A; Rapoport, S I

    1996-01-01

    OBJECTIVES--To examine cerebral metabolism, cognitive performance, and brain volumes in healthy controls and two groups of patients with probable Alzheimer's disease, one group with severe abnormalities of white matter (DAT+) and the other group with none, or minimal abnormalities (DAT-). METHODS--Neuropsychological tests, CT, MRI, quantitative MRI, and PET studies were carried out to allow comparison between the DAT+ and DAT- groups and the healthy controls. RESULTS--Compared with the healthy controls, both demented groups had significantly reduced global and regional cerebral metabolism, significant brain atrophy, and significantly lower scores on neuropsychological testing. The DAT- patient group showed a pattern of parietal-temporal cerebral metabolic reductions and neuropsychological performance deficits typical of Alzheimer's disease. In addition, metabolism in the association neocortex (AD ratio) and measures of neuropsychological task performance were significantly correlated in the DAT- patient group. Comparison of DAT+ with DAT- patients showed a significantly higher ratio of parietal to whole brain glucose utilisation for the DAT+ group. Moreover, when comparing group z score differences from the healthy controls, the DAT+ group had, on average, smaller differences from controls in the frontal, parietal, and temporal regions than did the DAT- group. Discriminant analysis using metabolic ratios of the frontal, parietal, and temporal regions showed cerebral metabolic patterns to be significantly different among the DAT+, the DAT-, and the healthy controls. These differences were due primarily to relatively higher frontal, parietal, and temporal metabolic ratios in the DAT+ group which resulted in discriminant scores for the DAT+ group between the healthy controls and the DAT- group. Group mean scores on tests of neuropsychological performance were not significantly different between the DAT- and DAT+ patients. By contrast with the DAT- group, however, no

  2. Regional homogeneity of resting-state brain abnormalities in violent juvenile offenders: a biomarker of brain immaturity?

    PubMed

    Chen, Chen; Zhou, Jiansong; Liu, Chunhong; Witt, Katrina; Zhang, Yingdong; Jing, Bin; Li, Chun; Wang, Xiaoping; Li, Lingjiang

    2015-01-01

    The authors investigated whether male violent juvenile offenders demonstrate any differences in local functional connectivity indicative of delayed maturation of the brain that may serve as a biomarker of violence. Twenty-nine violent juvenile offenders and 28 age-matched controls were recruited. Regional homogeneity (ReHo) method was used to analyze resting-state magnetic resonance images. Violent offenders showed significantly lower ReHo values in the right caudate, right medial prefrontal cortex, and left precuneus, and higher values in the right supramarginal gyrus than the controls. These regions had both high sensitivity and specificity in distinguishing between the two groups suggesting that dysfunction in these regions can be used to correctly classify those individuals who are violent. Dysfunction in the right medial prefrontal-caudate circuit may, therefore, represent an important biomarker of violence juvenile males. PMID:25716485

  3. Asymmetric Di-methyl Arginine is Strongly Associated with Cognitive Dysfunction and Brain MR Spectroscopic Abnormalities in Cirrhosis

    PubMed Central

    Bajaj, Jasmohan S; Ahluwalia, Vishwadeep; Wade, James B; Sanyal, Arun J; White, Melanie B; Noble, Nicole A; Monteith, Pamela; Fuchs, Michael; Sterling, Richard K; Luketic, Velimir; Bouneva, Iliana; Stravitz, Richard T; Puri, Puneet; Kraft, Kenneth A; Gilles, HoChong; Heuman, Douglas M

    2012-01-01

    Background Asymmetric di-methyl arginine (ADMA) is an inhibitor of nitric oxide synthase that accumulates in liver disease and may contribute to hepatic encephalopathy(HE). Aim To evaluate the association of ADMA with cognition and brain MR spectroscopy(MRS) in cirrhosis. Methods Cirrhotic patients with/without prior HE and non-cirrhotic controls underwent cognitive testing and ADMA determination. A subgroup underwent brain MRS [Glutamine/glutamate(Glx), myoinositol(mI), N-acetyl-aspartate(NAA) in parietal white, occipital gray and anterior cingulate(ACC)]. We also tested cognition and ADMA in a cirrhotic subgroup before and 1 month after transjugular intrahepatic portosystemic shunting (TIPS). Cognition and MRS values were correlated with ADMA and compared between groups using multi-variable regression. ADMA levels were compared between those who did/did not develop post-TIPS HE. Results 90 cirrhotics (MELD13, 54 prior HE) and 16 controls were included. Controls had better cognition and lower ADMA, Glx and higher mI compared to cirrhotics. Prior HE patients had worse cognition, higher ADMA and Glx and lower mI compared to non-HE cirrhotics. ADMA was positively correlated with MELD (r=0.58,p<0.0001), abnormal cognitive test number(r=0.66,p<0.0001) and Glx and NAAA (white matter,ACC) and negatively with mI. On regression, ADMA predicted number of abnormal tests and mean Z-score independent of prior HE and MELD. 12 patients underwent TIPS;7 developed HE post-TIPS. ADMA increased post-TIPS in patients who developed HE(p=0.019) but not in others(p=0.89). Conclusions A strong association of ADMA with cognition and prior HE was found independent of MELD score in cirrhosis. PMID:22889958

  4. Brief Report: The Role of National Brain and Tissue Banks in Research on Autism and Developmental Disorders.

    ERIC Educational Resources Information Center

    Zielke, H. Ronald; And Others

    1996-01-01

    This paper describes the establishment and work of two brain and tissue banks, which collect brain and other tissues from newly deceased individuals with autism and make these tissues available to researchers. Issues in tissue collection are identified, including the importance of advance planning, religious concerns of families, and the need for…

  5. Mimicking brain tissues by doping scatterers into gelatin tissue phantoms and determination of chemical species responsible for NMPPAS

    NASA Astrophysics Data System (ADS)

    Dahal, Sudhir; Cullum, Brian M.

    2012-06-01

    It has been shown that non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) has a great potential to be used as a high resolution surgical guidance technique during brain tumor surgery due to its ability of non-invasive or minimally invasive tumor differentiation. However, for experimental purposes associated with method validation, the use of real tissues is not always ideal because of issues such as availability, safety, storage, chemical doping, necessary control of size and shape, etc. To overcome these issues, tissue phantoms made from animal tissues and/or biochemical constituents, are often employed for such analyses. This work demonstrates the ability to develop and characterize gelatin based tissue phantoms with comparable optical and acoustic properties to real tissues by doping the phantoms with a scattering substance, 0.3 μm diameter Al2O3 particles. Using these phantoms, light scattering coefficients (μs) of 39 cm-1 have been generated, which are comparable to real brain tissue, thus making them a great alternative to real tissue for validation studies. In addition, this work also investigates the non-fluorescent species NAD+ found in the tissues, to evaluate its potential for being detected by NMPPAS. NMPPAS spectra of NAD+ shows a very promising beginning to determine other chemical species such as flavins, collagen, tryptophan, etc responsible for NMPPAS spectral signatures, associated with tumorogenesis.

  6. Docosahexaenoic acid reduces ER stress and abnormal protein accumulation and improves neuronal function following traumatic brain injury.

    PubMed

    Begum, Gulnaz; Yan, Hong Q; Li, Liaoliao; Singh, Amneet; Dixon, C Edward; Sun, Dandan

    2014-03-01

    In this study, we investigated the development of endoplasmic reticulum (ER) stress after traumatic brain injury (TBI) and the efficacy of post-TBI administration of docosahexaenoic acid (DHA) in reducing ER stress. TBI was induced by cortical contusion injury in Sprague-Dawley rats. Either DHA (16 mg/kg in DMSO) or vehicle DMSO (1 ml/kg) was administered intraperitoneally at 5 min after TBI, followed by a daily dose for 3-21 d. TBI triggered sustained expression of the ER stress marker proteins including phosphorylated eukaryotic initiation factor-2α, activating transcription factor 4, inositol requiring kinase 1, and C/EBP homologous protein in the ipsilateral cortex at 3-21 d after TBI. The prolonged ER stress was accompanied with an accumulation of abnormal ubiquitin aggregates and increased expression of amyloid precursor protein (APP) and phosphorylated tau (p-Tau) in the frontal cortex after TBI. The ER stress marker proteins were colocalized with APP accumulation in the soma. Interestingly, administration of DHA attenuated all ER stress marker proteins and reduced the accumulation of both ubiquitinated proteins and APP/p-Tau proteins. In addition, the DHA-treated animals exhibited early recovery of their sensorimotor function after TBI. In summary, our study demonstrated that TBI induces a prolonged ER stress, which is positively correlated with abnormal APP accumulation. The sustained ER stress may play a role in chronic neuronal damage after TBI. Our findings illustrate that post-TBI administration of DHA has therapeutic potentials in reducing ER stress, abnormal protein accumulation, and neurological deficits. PMID:24599472

  7. A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

    PubMed Central

    Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

    2013-01-01

    Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

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

    NASA Astrophysics Data System (ADS)

    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.

  9. Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

    PubMed

    Minkova, Lora; Eickhoff, Simon B; Abdulkadir, Ahmed; Kaller, Christoph P; Peter, Jessica; Scheller, Elisa; Lahr, Jacob; Roos, Raymund A; Durr, Alexandra; Leavitt, Blair R; Tabrizi, Sarah J; Klöppel, Stefan

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel-based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre-specified motor, working memory, cognitive flexibility, and social-affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre-HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre-HD were observed, but increased positive correlations were evident for mHD, relative to pre-HD and HC. These findings could be explained by a HD-related neuronal loss heterogeneously affecting the examined network at the pre-HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow-up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs. PMID:26453902

  10. Abnormal Brain Activity in Social Reward Learning in Children with Autism Spectrum Disorder: An fMRI Study

    PubMed Central

    Choi, Uk-Su; Kim, Sun-Young; Sim, Hyeon Jeong; Lee, Seo-Young; Park, Sung-Yeon; Jeong, Joon-Sup; Seol, Kyeong In; Yoon, Hyo-Woon; Jhung, Kyungun; Park, Jee-In

    2015-01-01

    Purpose We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). Materials and Methods 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. Results ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyrus. Conclusion These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs. PMID:25837176

  11. Apathy is associated with white matter abnormalities in anterior, medial brain regions in persons with HIV infection

    PubMed Central

    Kamat, Rujvi; Brown, Gregory G.; Bolden, Khalima; Fennema-Notestine, Christine; Archibald, Sarah; Marcotte, Thomas D.; Letendre, Scott L.; Ellis, Ronald J.; Woods, Steven Paul; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Apathy is a relatively common psychiatric syndrome in HIV infection, but little is known about its neural correlates. In the present study, we examined the associations between apathy and diffusion tensor imaging (DTI) indices in key frontal white matter regions in the thalamocorticostriatal circuit that has been implicated in the expression of apathy. Nineteen participants with HIV infection and 19 demographically comparable seronegative comparison subjects completed the Apathy subscale of the Frontal Systems Behavioral Scale as a part of a comprehensive neuropsychiatric research evaluation. When compared to the seronegative participants, the HIV+ group had significantly more frontal white matter abnormalities. Within HIV+ persons, and as predicted, higher ratings of apathy were associated with greater white matter alterations in the anterior corona radiata, genu, and orbital medial prefrontal cortex. The associations between white matter alterations and apathy were independent of depression and were stronger among participants with lower current CD4 counts. All told, these findings indicate that apathy is independently associated with white matter abnormalities in anterior, medial brain regions in persons infected with HIV, particularly in the setting of lower current immune functioning, which may have implications for antiretroviral therapy. PMID:25275424

  12. Steroid abnormalities and the developing brain: Declarative memory for emotionally arousing and neutral material in children with congenital adrenal hyperplasia

    PubMed Central

    Maheu, Françoise S.; Merke, Deborah P.; Schroth, Elizabeth A.; Keil, Margaret F.; Hardin, Julie; Poeth, Kaitlin; Pine, Daniel S.; Ernst, Monique

    2008-01-01

    Summary Steroid hormones modulate memory in animals and human adults. Little is known on the developmental effect of these hormones on the neural networks underlying memory. Using Congenital Adrenal Hyperplasia (CAH) as a naturalistic model of early steroid abnormalities, this study examines the consequences of CAH on memory and its neural correlates for emotionally arousing and neutral material in children. Seventeen patients with CAH and 17 age- and sex-matched healthy children (ages 12 to 14 years) completed the study. Subjects were presented positive, negative and neutral pictures. Memory recall occurred about 30 minutes after viewing the pictures. Children with CAH showed memory deficits for negative pictures compared to healthy children (p < 0.01). There were no group differences on memory performance for either positive or neutral pictures (p’s >0.1). In patients, 24h urinary-free cortisol levels (reflecting glucocorticoid replacement therapy) and testosterone levels were not associated with memory performance. These findings suggest that early steroid imbalances affect memory for negative material in children with CAH. Such memory impairments may result from abnormal brain organization and function following hormonal dysfunction during critical periods of development. PMID:18162329

  13. Intracranial Intra-arachnoid Diverticula and Cyst-like Abnormalities of the Brain.

    PubMed

    Platt, Simon; Hicks, Jill; Matiasek, Lara

    2016-03-01

    Primary intracranial cystic or cyst-like lesions include intra-arachnoid, epidermoid, dermoid, and choroid plexus cysts. Differentiation of these cystic lesions can usually be accomplished by imaging studies alone; however, some cysts are similar in appearance and require histopathology for definitive diagnosis. Clinical signs often reflect the location of the cysts within the intracranial cavity rather than the type of cyst. If clinical signs are significant and progressive, surgical removal is warranted and may be successful, although cystic contents could be harmful if allowed to contact surrounding brain parenchyma or meninges. PMID:26704659

  14. Tspyl2 Loss-of-Function Causes Neurodevelopmental Brain and Behavior Abnormalities in Mice.

    PubMed

    Li, Qi; Chan, Siu Yuen; Wong, Kwun K; Wei, Ran; Leung, Yu On; Ding, Abby Y; Hui, Tomy C K; Cheung, Charlton; Chua, Siew E; Sham, Pak C; Wu, Ed X; McAlonan, Grainne M

    2016-07-01

    Testis specific protein, Y-encoded-like 2 (TSPYL2) regulates the expression of genes encoding glutamate receptors. Glutamate pathology is implicated in neurodevelopmental conditions such as autism spectrum disorder, attention deficit hyperactivity disorder (ADHD) and schizophrenia. In line with this, a microduplication incorporating the TSPYL2 locus has been reported in people with ADHD. However, the role of Tspyl2 remains unclear. Therefore here we used a Tspyl2 loss-of-function mouse model to directly examine how this gene impacts upon behavior and brain anatomy. We hypothesized that Tspyl2 knockout (KO) would precipitate a phenotype relevant to neurodevelopmental conditions. In line with this prediction, we found that Tspyl2 KO mice were marginally more active, had significantly impaired prepulse inhibition, and were significantly more 'sensitive' to the dopamine agonist amphetamine. In addition, the lateral ventricles were significantly smaller in KO mice. These findings suggest that disrupting Tspyl2 gene expression leads to behavioral and brain morphological alterations that mirror a number of neurodevelopmental psychiatric traits. PMID:26826030

  15. Post mTBI fatigue is associated with abnormal brain functional connectivity

    PubMed Central

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants’ fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject’s fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  16. Post mTBI fatigue is associated with abnormal brain functional connectivity.

    PubMed

    Nordin, Love Engström; Möller, Marika Christina; Julin, Per; Bartfai, Aniko; Hashim, Farouk; Li, Tie-Qiang

    2016-01-01

    This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system. PMID:26878885

  17. Automatic recognition and analysis of synapses. [in brain tissue

    NASA Technical Reports Server (NTRS)

    Ungerleider, J. A.; Ledley, R. S.; Bloom, F. E.

    1976-01-01

    An automatic system for recognizing synaptic junctions would allow analysis of large samples of tissue for the possible classification of specific well-defined sets of synapses based upon structural morphometric indices. In this paper the three steps of our system are described: (1) cytochemical tissue preparation to allow easy recognition of the synaptic junctions; (2) transmitting the tissue information to a computer; and (3) analyzing each field to recognize the synapses and make measurements on them.

  18. Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

    PubMed

    Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

    2016-04-01

    Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

  19. A small number of abnormal brain connections predicts adult autism spectrum disorder

    PubMed Central

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez Sr, José E.; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  20. A small number of abnormal brain connections predicts adult autism spectrum disorder.

    PubMed

    Yahata, Noriaki; Morimoto, Jun; Hashimoto, Ryuichiro; Lisi, Giuseppe; Shibata, Kazuhisa; Kawakubo, Yuki; Kuwabara, Hitoshi; Kuroda, Miho; Yamada, Takashi; Megumi, Fukuda; Imamizu, Hiroshi; Náñez, José E; Takahashi, Hidehiko; Okamoto, Yasumasa; Kasai, Kiyoto; Kato, Nobumasa; Sasaki, Yuka; Watanabe, Takeo; Kawato, Mitsuo

    2016-01-01

    Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum. PMID:27075704

  1. Deficiency of the Chromatin Regulator Brpf1 Causes Abnormal Brain Development*

    PubMed Central

    You, Linya; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R.; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-01-01

    Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively. The MORF gene is mutated in four neurodevelopmental disorders sharing the characteristic of intellectual disability and frequently displaying callosal agenesis. Here, we report that forebrain-specific inactivation of the mouse Brpf1 gene caused early postnatal lethality, neocortical abnormalities, and partial callosal agenesis. With respect to the control, the mutant forebrain contained fewer Tbr2-positive intermediate neuronal progenitors and displayed aberrant neurogenesis. Molecularly, Brpf1 loss led to decreased transcription of multiple genes, such as Robo3 and Otx1, important for neocortical development. Surprisingly, elevated expression of different Hox genes and various other transcription factors, such as Lhx4, Foxa1, Tbx5, and Twist1, was also observed. These results thus identify an important role of Brpf1 in regulating forebrain development and suggest that it acts as both an activator and a silencer of gene expression in vivo. PMID:25568313

  2. Deficiency of the chromatin regulator BRPF1 causes abnormal brain development.

    PubMed

    You, Linya; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-03-13

    Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively. The MORF gene is mutated in four neurodevelopmental disorders sharing the characteristic of intellectual disability and frequently displaying callosal agenesis. Here, we report that forebrain-specific inactivation of the mouse Brpf1 gene caused early postnatal lethality, neocortical abnormalities, and partial callosal agenesis. With respect to the control, the mutant forebrain contained fewer Tbr2-positive intermediate neuronal progenitors and displayed aberrant neurogenesis. Molecularly, Brpf1 loss led to decreased transcription of multiple genes, such as Robo3 and Otx1, important for neocortical development. Surprisingly, elevated expression of different Hox genes and various other transcription factors, such as Lhx4, Foxa1, Tbx5, and Twist1, was also observed. These results thus identify an important role of Brpf1 in regulating forebrain development and suggest that it acts as both an activator and a silencer of gene expression in vivo. PMID:25568313

  3. Facial emotion recognition impairments are associated with brain volume abnormalities in individuals with HIV.

    PubMed

    Clark, Uraina S; Walker, Keenan A; Cohen, Ronald A; Devlin, Kathryn N; Folkers, Anna M; Pina, Matthew J; Tashima, Karen T

    2015-04-01

    Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV-associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities. PMID:25744868

  4. Persistent frontal P300 brain potential suggests abnormal processing of auditory information in distractible children.

    PubMed

    Kilpeläinen, R; Luoma, L; Herrgård, E; Yppärilä, H; Partanen, J; Karhu, J

    1999-11-01

    The P300 event-related potential (ERP) was studied at the beginning, in the middle, and at the end of an auditory stimulus discrimination task in 70 normal 9-year-old children. Easily distractible children showed frontally a short-latency P300 response to target stimuli throughout the task, whereas in the non-distractible children the corresponding response was distinctly smaller and also showed a tendency to decrease in size towards the end of the task. The short-latency frontal P300 response reflects activation of the brain's orienting networks, and it normally decreases in size when stimuli lose their 'novelty value' with stimulus repetition. Persistent frontal P300 suggest that distractible children continued to show enhanced orienting to stimuli that should have already been well encoded and/or categorized. PMID:10599853

  5. Myoinositol and glutamate complex neurometabolite abnormality after mild traumatic brain injury

    PubMed Central

    Kierans, Andrea S.; Kirov, Ivan I.; Gonen, Oded; Haemer, Gillian; Nisenbaum, Eric; Babb, James S.; Grossman, Robert I.

    2014-01-01

    Objective: To obtain quantitative neurometabolite measurements, specifically myoinositol (mI) and glutamate plus glutamine (Glx), markers of glial and neuronal excitation, in deep gray matter structures after mild traumatic brain injury (mTBI) using proton magnetic resonance spectroscopy (1H-MRS) and to compare these measurements against normal healthy control subjects. Methods: This study approved by the institutional review board is Health Insurance Portability and Accountability Act compliant. T1-weighted MRI and multi-voxel 1H-MRS imaging were acquired at 3 tesla from 26 patients with mTBI an average of 22 days postinjury and from 13 age-matched healthy controls. Two-way analysis of variance was used to compare patients and controls for mean N-acetylaspartate, choline, creatine (Cr), Glx, and mI levels as well as the respective ratios to Cr within the caudate, globus pallidus, putamen, and thalamus. Results: Quantitative putaminal mI was higher in patients with mTBI compared with controls (p = 0.02). Quantitative neurometabolite ratios of putaminal mI and Glx relative to Cr, mI/Cr, and Glx/Cr were also higher among patients with mTBI compared with controls (p = 0.01 and 0.02, respectively). No other differences in neurometabolite levels or ratios were observed in any other brain region evaluated. Conclusion: Increased putaminal mI, mI/Cr, and Glx/Cr in patients after mTBI compared with control subjects supports the notion of a complex glial and excitatory response to injury without concomitant neuronal loss, evidenced by preserved N-acetylaspartate levels in this region. PMID:24401686

  6. Novel Molecular Pathways Elicited by Mutant FGFR2 May Account for Brain Abnormalities in Apert Syndrome

    PubMed Central

    Yeh, Erika; Fanganiello, Roberto D.; Sunaga, Daniele Y.; Zhou, Xueyan; Holmes, Gregory; Rocha, Katia M.; Alonso, Nivaldo; Matushita, Hamilton; Wang, Yingli; Jabs, Ethylin W.; Passos-Bueno, Maria Rita

    2013-01-01

    Apert syndrome (AS), the most severe form craniosynostosis, is characterized by premature fusion of coronal sutures. Approximately 70% of AS patients carry S252W gain-of-function mutation in FGFR2. Besides the cranial phenotype, brain dysmorphologies are present and are not seen in other FGFR2-asociated craniosynostosis, such as Crouzon syndrome (CS). Here, we hypothesized that S252W mutation leads not only to overstimulation of FGFR2 downstream pathway, but likewise induces novel pathological signaling. First, we profiled global gene expression of wild-type and S252W periosteal fibroblasts stimulated with FGF2 to activate FGFR2. The great majority (92%) of the differentially expressed genes (DEGs) were divergent between each group of cell populations and they were regulated by different transcription factors. We than compared gene expression profiles between AS and CS cell populations and did not observe correlations. Therefore, we show for the first time that S252W mutation in FGFR2 causes a unique cell response to FGF2 stimulation. Since our gene expression results suggested that novel signaling elicited by mutant FGFR2 might be associated with central nervous system (CNS) development and maintenance, we next investigated if DEGs found in AS cells were also altered in the CNS of an AS mouse model. Strikingly, we validated Strc (stereocilin) in newborn Fgfr2S252W/+ mouse brain. Moreover, immunostaining experiments suggest a role for endothelial cells and cerebral vasculature in the establishment of characteristic CNS dysmorphologies in AS that has not been proposed by previous literature. Our approach thus led to the identification of new target genes directly or indirectly associated with FGFR2 which are contributing to the pathophysiology of AS. PMID:23593218

  7. Abnormal intrinsic brain activity patterns in leukoaraiosis with and without cognitive impairment.

    PubMed

    Li, Chuanming; Yang, Jun; Yin, Xuntao; Liu, Chen; Zhang, Lin; Zhang, Xiaochun; Gui, Li; Wang, Jian

    2015-10-01

    The amplitude of low frequency fluctuations (ALFF) from resting-state functional MRI (rs-fMRI) signals can be used to detect intrinsic spontaneous brain activity and provide valuable insights into the pathomechanism of neural disease. In this study, we recruited 56 patients who had been diagnosed as having mild to severe leukoaraiosis. According to the neuropsychological tests, they were subdivided into a leukoaraiosis with cognitive impairment group (n = 28) and a leukoaraiosis without cognitive impairment group (n = 28). 28 volunteers were included as normal controls. We found that the three groups showed significant differences in ALFF in the brain regions of the right inferior occipital gyrus (IOG_R), left middle temporal gyrus (MTG_L), left precuneus (Pcu_L), right superior frontal gyrus (SFG_R) and right superior occipital gyrus (SOG_R). Compared with normal controls, the leukoaraiosis without cognitive impairment group exhibited significantly increased ALFF in the IOG_R, Pcu_L, SFG_R and SOG_R. While compared with leukoaraiosis without cognitive impairment group, the leukoaraiosis with cognitive impairment group showed significantly decreased ALFF in IOG_R, MTG_L, Pcu_L and SOG_R. A close negative correlation was found between the ALFF values of the MTG_L and the Montreal Cognitive Assessment (MoCA) scores. Our data demonstrate that white matter integrity and cognitive impairment are associated with different amplitude fluctuations of rs-fMRI signals. Leukoaraiosis is related to ALFF increases in IOG_R, Pcu_L, SFG_Orb_R and SOG_R. Decreased ALFF in MTG_L is characteristic of cognitive impairment and may aid in its early detection. PMID:26116811

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

    NASA Astrophysics Data System (ADS)

    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 < 0.05) compared to non-compliant silicon and PVAc-coated silicon materials. Furthermore, both PVAc-coated non-compliant silicon and compliant nanocomposite shanks showed significantly reduced (by 4-5 fold) stresses due to tissue micromotion at the interface. Significance. The results of this study showed that soft, adaptive materials reduce strains and strain rates and micromotion induced stresses in the surrounding brain tissue

  9. Compliant Intracortical Implants Reduce Strains and Strain Rates in Brain Tissue In Vivo

    PubMed Central

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

    2015-01-01

    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 sec 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<0.05) compared to non-compliant silicon and PVAc-coated silicon materials. Further, both PVAc-coated non-compliant silicon and compliant nanocomposite shanks showed significantly reduced (by 4–5 fold) stresses due to tissue micromotion at the interface. Significance The results of this study showed that soft, adaptive materials reduce strains and strain rates and micromotion induced stresses in the surrounding brain tissue

  10. Abnormal regional cerebral blood flow found by technetium-99m ethyl cysteinate dimer brain single photon emission computed tomography in systemic lupus erythematosus patients with normal brain MRI findings.

    PubMed

    Chen, J J-H; Yen, R-F; Kao, A; Lin, C-C; Lee, C-C

    2002-11-01

    In this study, technetium-(99m) ethyl cysteinate dimer ((99m)Tc ECD) brain single photon emission computed tomography (SPECT) was used to detect regional cerebral blood flow (rCBF) of the brain in SLE patients with normal brain magnetic resonance imaging (MRI) findings. Twenty female SLE patients were enrolled in this study, divided into two groups. Group 1 consisted of 10 patients with neuropsychiatric manifestations. Group 2 consisted of 10 patients without neuropsychiatric manifestations. All patients had normal brain MRI findings. Another 10 SLE patients with abnormal MRI findings were included as group 3 for comparison. Meanwhile, 10 healthy female volunteers also underwent brain MRI and (99m)Tc ECD brain SPECT for comparison. The scans revealed hypoperfusion lesions in 9/20 (45%) SLE patients, including 7/10 (70%) cases in group 1 and 2/10 (20%) cases in group 2. In contrast, all 10 patients (100%) in group 3 had abnormal (99m)Tc ECD brain SPECT findings. The parietal lobes were the most commonly involved areas. We conclude that (99m)Tc ECD brain SPECT is more sensitive for detecting rCBF changes than is brain MRI in detecting the brain anatomic changes, and may have a diagnostic value in lupus cerebral involvement. However, (99m)Tc ECD brain SPECT may not be indicated for SLE patients with normal MRI and mild neuropsychiatric symptoms/signs, such headaches and dizziness. PMID:12447638

  11. Left Atrial Volumes and Reservoir Function Are Associated With Subclinical Cerebrovascular Disease: The Cardiovascular Abnormalities and Brain Lesions (CABL) Study

    PubMed Central

    Russo, Cesare; Jin, Zhezhen; Liu, Rui; Iwata, Shinichi; Tugcu, Aylin; Yoshita, Mitsuhiro; Homma, Shunichi; Elkind, Mitchell S.V.; Rundek, Tatjana; DeCarli, Charles; Wright, Clinton B.; Sacco, Ralph L.; Di Tullio, Marco R.

    2013-01-01

    Objectives To assess the relationship of left atrial (LA) phasic volumes and LA reservoir function with subclinical cerebrovascular disease in a stroke-free community-based cohort. Background An increase in LA size is associated with cardiovascular events including stroke. However, it is not known whether LA phasic volumes and reservoir function are associated with subclinical cerebrovascular disease. Methods LA minimum (LAVmin) and maximum (LAVmax) volumes, and LA reservoir function, measured as total emptying volume (LAEV) and total emptying fraction (LAEF), were assessed by real-time three-dimensional echocardiography in 455 stroke-free participants from the community-based Cardiovascular Abnormalities and Brain Lesions (CABL) study. Subclinical cerebrovascular disease was assessed as silent brain infarcts (SBI) and white matter hyperintensity volume (WMHV) by brain magnetic resonance imaging (MRI). Results SBI prevalence was 15.4%; mean WMHV was 0.66±0.92%. Participants with SBI showed greater LAVmin (17.1±9.3 vs. 12.5±5.6 ml/m2, p<0.01) and LAVmax (26.6±8.8 vs. 23.3±7.0 ml/m2, p<0.01) compared to those without SBI. LAEV (9.5±3.4 vs. 10.8±3.9 ml/m2, p<0.01) and LAEF (38.7±14.7% vs. 47.0±11.9%, p<0.01) were also reduced in participants with SBI. In univariate analyses, greater LA volumes and smaller reservoir function were significantly associated with greater WMHV. In multivariate analyses, LAVmin remained significantly associated with SBI [adjusted odds ratio (OR) per SD increase: 1.37, 95% confidence intervals (CI) 1.04–1.80, p<0.05] and with WMHV (β=0.12, p<0.01), whereas LAVmax was not independently associated with either. Smaller LAEF was independently associated with SBI (adjusted OR=0.67, 95% CI 0.50–0.90, p<0.01) and WMHV (β=−0.09, p<0.05). Conclusions Greater LA volumes and reduced LA reservoir function are associated with subclinical cerebrovascular disease detected by brain MRI in subjects without history of stroke. LAVmin and LAEF

  12. In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

    PubMed

    Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

    2016-05-01

    High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining. PMID:26830089

  13. Evaluation of three-dimensional anisotropic head model for mapping realistic electromagnetic fields of brain tissues

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    Electromagnetic fields provide fundamental data for the imaging of electrical tissue properties, such as conductivity and permittivity, in recent magnetic resonance (MR)-based tissue property mapping. The induced voltage, current density, and magnetic flux density caused by externally injected current are critical factors for determining the image quality of electrical tissue conductivity. As a useful tool to identify bio-electromagnetic phenomena, precise approaches are required to understand the exact responses inside the human body subject to an injected currents. In this study, we provide the numerical simulation results of electromagnetic field mapping of brain tissues using a MR-based conductivity imaging method. First, we implemented a realistic three-dimensional human anisotropic head model using high-resolution anatomical and diffusion tensor MR images. The voltage, current density, and magnetic flux density of brain tissues were imaged by injecting 1 mA of current through pairs of electrodes on the surface of our head model. The current density map of anisotropic brain tissues was calculated from the measured magnetic flux density based on the linear relationship between the water diffusion tensor and the electrical conductivity tensor. Comparing the current density to the previous isotropic model, the anisotropic model clearly showed the differences between the brain tissues. This originates from the enhanced signals by the inherent conductivity contrast as well as the actual tissue condition resulting from the injected currents.

  14. Expanded CTG repeat demarcates a boundary for abnormal CpG methylation in myotonic dystrophy patient tissues

    PubMed Central

    López Castel, Arturo; Nakamori, Masayuki; Tomé, Stephanie; Chitayat, David; Gourdon, Geneviève; Thornton, Charles A.; Pearson, Christopher E.

    2011-01-01

    Myotonic dystrophy (DM1) affects multiple organs, shows age-dependent progression and is caused by CTG expansions at the DM1 locus. We determined the DM1 CpG methylation profile and CTG length in tissues from DM1 foetuses, DM1 adults, non-affected individuals and transgenic DM1 mice. Analysis included CTCF binding sites upstream and downstream of the CTG tract, as methylation-sensitive CTCF binding affects chromatinization and transcription of the DM1 locus. In humans, in a given foetus, expansions were largest in heart and smallest in liver, differing by 40–400 repeats; in adults, the largest expansions were in heart and cerebral cortex and smallest in cerebellum, differing by up to 5770 repeats in the same individual. Abnormal methylation was specific to the mutant allele. In DM1 adults, heart, liver and cortex showed high-to-moderate methylation levels, whereas cerebellum, kidney and skeletal muscle were devoid of methylation. Methylation decreased between foetuses and adults. Contrary to previous findings, methylation was not restricted to individuals with congenital DM1. The expanded repeat demarcates an abrupt boundary of methylation. Upstream sequences, including the CTCF site, were methylated, whereas the repeat itself and downstream sequences were not. In DM1 mice, expansion-, tissue- and age-specific methylation patterns were similar but not identical to those in DM1 individuals; notably in mice, methylation was present up- and downstream of the repeat, but greater upstream. Thus, in humans, the CpG-free expanded CTG repeat appears to maintain a highly polarized pattern of CpG methylation at the DM1 locus, which varies markedly with age and tissues. PMID:21044947

  15. Influence of preservation temperature on the measured mechanical properties of brain tissue.

    PubMed

    Rashid, Badar; Destrade, Michel; Gilchrist, Michael D

    2013-04-26

    The large variability in experimentally measured mechanical properties of brain tissue is due to many factors including heterogeneity, anisotropy, age dependence and post-mortem time. Moreover, differences in test protocols also influence these measured properties. This paper shows that the temperature at which porcine brain tissue is stored or preserved prior to testing has a significant effect on the mechanical properties of brain tissue, even when tests are conducted at the same temperatures. Three groups of brain tissue were stored separately for at least 1h at three different preservation temperatures, i.e., ice cold, room temperature (22 °C) and body temperature (37 °C), prior to them all being tested at room temperature (~22 °C). Significant differences in the corresponding initial elastic shear modulus μ (Pa) (at various amounts of shear, 0≤K≤1.0) were observed. The initial elastic moduli were 1043±271 Pa, 714±210 Pa and 497±156 Pa (mean±SD) at preservation temperatures of ice cold, 22 °C and 37 °C, respectively. Based on this investigation, it is strongly recommended that brain tissue samples must be preserved at an ice-cold temperature prior to testing in order to minimize the difference between the measured in vitro test results and the in vivo properties. A by-product of the study is that simple shear tests allow for large, almost perfectly homogeneous deformation of brain matter. PMID:23523381

  16. Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

    PubMed

    Shoemaker, Ritchie C; House, Dennis; Ryan, James C

    2014-01-01

    Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation

  17. Stress response of bovine artery and rat brain tissue due to combined translational shear and fixed unconfined compression

    NASA Astrophysics Data System (ADS)

    Leahy, Lauren

    During trauma resulting from impacts and blast waves, sinusoidal waves permeate the brain and cranial arterial tissue, both non-homogeneous biological tissues with high fluid contents. The experimental shear stress response to sinusoidal translational shear deformation at 1 Hz and 25% strain amplitude and either 0% or 33% compression is compared for rat brain tissue and bovine aortic tissue. Both tissues exhibit Mullins effect in shear. Harmonic wavelet decomposition, a novel application to the mechanical response of these tissues, shows significant 1 Hz and 3 Hz components. The 3 Hz component magnitude in brain tissue, which is much larger than in aortic tissue, may correlate to interstitial fluid induced drag forces that decrease on subsequent cycles perhaps because of damage resulting in easier fluid movement. The fluid may cause the quasiperiodic, viscoelastic behavior of brain tissue. The mechanical response differences under impact may cause shear damage between arterial and brain connections.

  18. Characterization of a Raman spectroscopy probe system for intraoperative brain tissue classification

    PubMed Central

    Desroches, Joannie; Jermyn, Michael; Mok, Kelvin; Lemieux-Leduc, Cédric; Mercier, Jeanne; St-Arnaud, Karl; Urmey, Kirk; Guiot, Marie-Christine; Marple, Eric; Petrecca, Kevin; Leblond, Frédéric

    2015-01-01

    A detailed characterization study is presented of a Raman spectroscopy system designed to maximize the volume of resected cancer tissue in glioma surgery based on in vivo molecular tissue characterization. It consists of a hand-held probe system measuring spectrally resolved inelastically scattered light interacting with tissue, designed and optimized for in vivo measurements. Factors such as linearity of the signal with integration time and laser power, and their impact on signal to noise ratio, are studied leading to optimal data acquisition parameters. The impact of ambient light sources in the operating room is assessed and recommendations made for optimal operating conditions. In vivo Raman spectra of normal brain, cancer and necrotic tissue were measured in 10 patients, demonstrating that real-time inelastic scattering measurements can distinguish necrosis from vital tissue (including tumor and normal brain tissue) with an accuracy of 87%, a sensitivity of 84% and a specificity of 89%. PMID:26203368

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

    PubMed

    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. PMID:26056378

  20. Experimental study on the toxicity of povidone-iodine solution in brain tissues of rabbits

    PubMed Central

    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 Povidone-iodine Solution (0.01%), in Group C and D, the right cerebral cortex of rabbits was also locally rinsed with Povidone-iodine Solution (0.05%). In Group A and C, the rabbits were sacrificed at D3 after the operation, and the brain was taken out; and in Group B and D, the rabbits were sacrificed at D7 after the operation, and the brain was taken out. Under the optical and electron microscope, the change in micro-structure of brain tissues was observed in each group. Results: In each group, there was no epilepsy or paralysis during and after the operation. At the treatment side of physiological saline, there was no significant cell damage in the local brain tissues. At the treatment side of Povidone-iodine Solution, there was no cell apoptosis or degeneration in the local brain tissues. Conclusion: The Povidone-iodine Solution (0.05% and 0.01%) was toxic to brain tissues, with a more obvious damage of brain tissues for the former concentration. The histological sign was more serious at D7 than that at D3. PMID:26628968

  1. A hybrid hierarchical approach for brain tissue segmentation by combining brain atlas and least square support vector machine.

    PubMed

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

    2013-10-01

    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

  2. Dopamine in thelimbic regions of the human brain: normal and abnormal.

    PubMed

    Farley, I J; Price, K S; Hornykiewicz, O

    1977-01-01

    1. In the human brain, DA was found in appreciable amounts in most of the examined basal telencephalic limbic regions, with the nucleus accumbens having the highest mean level (3.38 microgram/g). In the cortical areas of the limbic lobe of Broca, DA could be measured with certainty only in the parolfactory gyrus (0.35 microgram/g). 2. In patients with Parkinson's disease, the DA concentration in the parolfactory gyrus and nucleur accumbens was markedly reduced, whereas little change was seen in the olfactory areas. Quantitatively, the DA decrease in the nucleus accumbens was of the same magnitude as in the caudate nucleus, being, in both regions, distinctly less severe than in the putamen. 3. In three cases of paranoid schizophrenia, there were no statistically significant changes of the mean levels of DA or HVA in the nucleus accumbens. However, the DA/HVA ratio was shifted noticeably in favor of HVA, possibly indicating an increase in DA turnover. This change was less pronounced in the putamen of these cases and was absent in the caudate nucleus. 4. The possibility of the substantia nigra contributing to the dopaminergic innervation of the human nucleus accumbens, as well as the significance of the observations on DA metabolism in the schizophrenic cases, is discussed. PMID:883559

  3. Automated Detection of Brain Abnormalities in Neonatal Hypoxia Ischemic Injury from MR Images

    PubMed Central

    Ghosh, Nirmalya; Sun, Yu; Bhanu, Bir; Ashwal, Stephen; Obenaus, Andre

    2014-01-01

    We compared the efficacy of three automated brain injury detection methods, namely symmetry-integrated region growing (SIRG), hierarchical region splitting (HRS) and modified watershed segmentation (MWS) in human and animal magnetic resonance imaging (MRI) datasets for the detection of hypoxic ischemic injuries (HII). Diffusion weighted imaging (DWI, 1.5T) data from neonatal arterial ischemic stroke (AIS) patients, as well as T2-weighted imaging (T2WI, 11.7T, 4.7T) at seven different time-points (1, 4, 7, 10, 17, 24 and 31 days post HII) in rat-pup model of hypoxic ischemic injury were used to check the temporal efficacy of our computational approaches. Sensitivity, specificity, similarity were used as performance metrics based on manual (‘gold standard’) injury detection to quantify comparisons. When compared to the manual gold standard, automated injury location results from SIRG performed the best in 62% of the data, while 29% for HRS and 9% for MWS. Injury severity detection revealed that SIRG performed the best in 67% cases while HRS for 33% data. Prior information is required by HRS and MWS, but not by SIRG. However, SIRG is sensitive to parameter-tuning, while HRS and MWS are not. Among these methods, SIRG performs the best in detecting lesion volumes; HRS is the most robust, while MWS lags behind in both respects. PMID:25000294

  4. Structural brain abnormalities in postural tachycardia syndrome: A VBM-DARTEL study

    PubMed Central

    Umeda, Satoshi; Harrison, Neil A.; Gray, Marcus A.; Mathias, Christopher J.; Critchley, Hugo D.

    2015-01-01

    Postural tachycardia syndrome (PoTS), a form of dysautonomia, is characterized by orthostatic intolerance, and is frequently accompanied by a range of symptoms including palpitations, lightheadedness, clouding of thought, blurred vision, fatigue, anxiety, and depression. Although the estimated prevalence of PoTS is approximately 5–10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) procedure to examine variation in regional brain structure associated with PoTS. We recruited 11 patients with established PoTS and 23 age-matched normal controls. Group comparison of gray matter volume revealed diminished gray matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients. Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients. PMID:25852449

  5. Optical imaging for brain tissue characterization using relative fluorescence lifetime imaging

    NASA Astrophysics Data System (ADS)

    Papour, Asael; Taylor, Zach; Sherman, Adria; Sanchez, Desiree; Lucey, Gregory; Liau, Linda; Stafsudd, Oscar; Yong, William; Grundfest, Warren

    2013-06-01

    An autofluorescence lifetime wide-field imaging system that can generate contrast in underlying tissue structures of normal and malignant brain tissue samples with video rate acquisition and processing time is presented. Images of the investigated tissues were acquired with high resolution (˜35 μm) using an algorithm to produce contrast based on differences in relative lifetimes. Sufficient contrast for delineation was produced without the computation of fluorescence decay times or Laguerre coefficients. The imaged tissues were sent for histological analysis that confirmed the detected imaged tissues morphological findings and correlations between relative lifetime maps and histology identified.

  6. Numerical analysis of the diffusive mass transport in brain tissues with applications to optical sensors

    NASA Astrophysics Data System (ADS)

    Neculae, Adrian P.; Otte, Andreas; Curticapean, Dan

    2013-03-01

    In the brain-cell microenvironment, diffusion plays an important role: apart from delivering glucose and oxygen from the vascular system to brain cells, it also moves informational substances between cells. The brain is an extremely complex structure of interwoven, intercommunicating cells, but recent theoretical and experimental works showed that the classical laws of diffusion, cast in the framework of porous media theory, can deliver an accurate quantitative description of the way molecules are transported through this tissue. The mathematical modeling and the numerical simulations are successfully applied in the investigation of diffusion processes in tissues, replacing the costly laboratory investigations. Nevertheless, modeling must rely on highly accurate information regarding the main parameters (tortuosity, volume fraction) which characterize the tissue, obtained by structural and functional imaging. The usual techniques to measure the diffusion mechanism in brain tissue are the radiotracer method, the real time iontophoretic method and integrative optical imaging using fluorescence microscopy. A promising technique for obtaining the values for characteristic parameters of the transport equation is the direct optical investigation using optical fibers. The analysis of these parameters also reveals how the local geometry of the brain changes with time or under pathological conditions. This paper presents a set of computations concerning the mass transport inside the brain tissue, for different types of cells. By measuring the time evolution of the concentration profile of an injected substance and using suitable fitting procedures, the main parameters characterizing the tissue can be determined. This type of analysis could be an important tool in understanding the functional mechanisms of effective drug delivery in complex structures such as the brain tissue. It also offers possibilities to realize optical imaging methods for in vitro and in vivo

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

    NASA Astrophysics Data System (ADS)

    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.

  8. A protein homeostasis signature in healthy brains recapitulates tissue vulnerability to Alzheimer’s disease

    PubMed Central

    Freer, Rosie; Sormanni, Pietro; Vecchi, Giulia; Ciryam, Prajwal; Dobson, Christopher M.; Vendruscolo, Michele

    2016-01-01

    In Alzheimer’s disease, aggregates of Aβ and tau in amyloid plaques and neurofibrillary tangles spread progressively across brain tissues following a characteristic pattern, implying a tissue-specific vulnerability to the disease. We report a transcriptional analysis of healthy brains and identify an expression signature that predicts—at ages well before the typical onset—the tissue-specific progression of the disease. We obtain this result by finding a quantitative correlation between the histopathological staging of the disease and the expression patterns of the proteins that coaggregate in amyloid plaques and neurofibrillary tangles, together with those of the protein homeostasis components that regulate Aβ and tau. Because this expression signature is evident in healthy brains, our analysis provides an explanatory link between a tissue-specific environmental risk of protein aggregation and a corresponding vulnerability to Alzheimer’s disease. PMID:27532054

  9. Using kinetic parameter analysis of dynamic FDOPA-PET for brain tissue classification

    NASA Astrophysics Data System (ADS)

    Lin, Hong-Dun; Lin, Kang-Ping; Chung, Being-Tau; Yu, Chin-Lung; Wang, Rong-Fa; Wu, Liang-Chi; Liu, Ren-Shyan

    2002-04-01

    In clinically, structural image based brain tissue segmentation as a preprocess plays an important and essential role on a number of image preprocessing, such as image visualization, object recognition, image registration, and so forth. However, when we need to classify the tissues according to their physiological functions, those strategies are not satisfactory. In this study, we incorporated both tissue time-activity curves (TACs) and derived kinetic parametric curves (KPCs) information to segment brain tissues, such as striatum, gray and white matters, in dynamic FDOPA-PET studies. Four common clustering techniques, K-mean (KM), Fuzzy C-mean (FCM), Isodata (ISO), Markov Random Fields (MRF), and our method were compared to evaluate its precision. The results show 41% and 48% less mean errors in mean difference for KPCs and TACs, respectively, than other methods. Combined KPCs and TACs based clustering method provide the ability to define brain structure effectively.

  10. A protein homeostasis signature in healthy brains recapitulates tissue vulnerability to Alzheimer's disease.

    PubMed

    Freer, Rosie; Sormanni, Pietro; Vecchi, Giulia; Ciryam, Prajwal; Dobson, Christopher M; Vendruscolo, Michele

    2016-08-01

    In Alzheimer's disease, aggregates of Aβ and tau in amyloid plaques and neurofibrillary tangles spread progressively across brain tissues following a characteristic pattern, implying a tissue-specific vulnerability to the disease. We report a transcriptional analysis of healthy brains and identify an expression signature that predicts-at ages well before the typical onset-the tissue-specific progression of the disease. We obtain this result by finding a quantitative correlation between the histopathological staging of the disease and the expression patterns of the proteins that coaggregate in amyloid plaques and neurofibrillary tangles, together with those of the protein homeostasis components that regulate Aβ and tau. Because this expression signature is evident in healthy brains, our analysis provides an explanatory link between a tissue-specific environmental risk of protein aggregation and a corresponding vulnerability to Alzheimer's disease. PMID:27532054

  11. Determination of the elasticity parameters of brain tissue with combined simulation and registration.

    PubMed

    Soza, G; Grosso, R; Nimsky, C; Hastreiter, P; Fahlbusch, R; Greiner, G

    2005-09-01

    Reliable elasticity parameters describing the behavior of a given material are an important issue in the context of physically-based simulation. In this paper we introduce a method for the determination of the mechanical properties of brain tissue. Elasticity parameters Young's modulus E and Poisson's ratio nu are estimated in an iterative framework coupling a finite element simulation with image registration. Within this framework, the outcome of the simulation is parameterized with both elasticity moduli that are automatically varied until optimal image correspondence between the simulated and the intraoperative data is achieved. We calculated optimal mechanical properties of brain tissue in six cases. The statistical analysis of the obtained values showed a good correlation of the results, thus proving the value of the method. An approach combining simulation and registration for the determination of the mechanical brain tissue properties is presented. This contributes to performing reliable physically-based simulation of soft tissue movement. PMID:17518395

  12. A case of ataxic diplegia, mental retardation, congenital nystagmus and abnormal auditory brain stem responses showing only waves I and II.

    PubMed

    Aiba, K; Yokochi, K; Ishikawa, T

    1986-01-01

    A three-year-old boy who had ataxic diplegia, mental retardation, horizontal pendular nystagmus with head nodding and abnormal auditory brain stem responses showing only waves I and II was presented. His clinical features coincided with recent reports in the Japanese literature of cases of a new syndrome that is congenital in origin and seen only in boys. PMID:3826555

  13. Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

    ERIC Educational Resources Information Center

    Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

  14. Effects of simulated microgravity on human brain nervous tissue.

    PubMed

    Wang, Xianghan; Du, Jianxin; Wang, Demei; Zeng, Fan; Wei, Yukui; Wang, Fuli; Feng, Chengcheng; Li, Nuomin; Dai, Rongji; Deng, Yulin; Quan, Zhenzhen; Qing, Hong

    2016-08-01

    During spaceflight, the negative effects of space microgravity on astronauts are becoming more and more prominent, and especially, of which on the nervous system is urgently to be solved. For this purpose tissue blocks and primary cells of nervous tissues obtained from glioma of patients were cultivated after culturing for about 7days, explanted tissues and cells were then randomly divided into two groups, one for static culture (control group, C), and the other for rotary processing for 1day, 3days, 5days, 7days and 14days (experiment group, E). Figures captured by inverted microscope revealed that, with short time rotating for 1day or 3days, morphology changes of tissue blocks were not obvious. When the rotary time was extended to 7days or 14days, it was found that cell somas is significantly larger and the ability of adhesion is declined in comparison with that in control group. Additionally, the arrangement of cells migrated from explanted tissues was disorganized, and the migration distance became shorter. In immunofluorescence analysis, β-tubulin filaments in control group appeared to organize into bundles. While in experiment group, β-tubulin was highly disorganized. In conclusion, simulated microgravity treatment for a week affected the morphology of nervous tissue, and caused highly disorganized distribution of cytoskeleton and the increase of cell apoptosis. These morphological changes might be one of the causes of apoptosis induced by simulated microgravity. PMID:27268042

  15. Clinical manifestations that predict abnormal brain computed tomography (CT) in children with minor head injury

    PubMed Central

    Alharthy, Nesrin; Al Queflie, Sulaiman; Alyousef, Khalid; Yunus, Faisel

    2015-01-01

    Background: Computed tomography (CT) used in pediatric pediatrics brain injury (TBI) to ascertain neurological manifestations. Nevertheless, this practice is associated with adverse effects. Reports in the literature suggest incidents of morbidity and mortality in children due to exposure to radiation. Hence, it is found imperative to search for a reliable alternative. Objectives: The aim of this study is to find a reliable clinical alternative to detect an intracranial injury without resorting to the CT. Materials and Methods: Retrospective cross-sectional study was undertaken in patients (1-14 years) with blunt head injury and having a Glasgow Coma Scale (GCS) of 13-15 who had CT performed on them. Using statistical analysis, the correlation between clinical examination and positive CT manifestation is analyzed for different age-groups and various mechanisms of injury. Results: No statistically significant association between parameteres such as Loss of Consciousness, ‘fall’ as mechanism of injury, motor vehicle accidents (MVA), more than two discrete episodes of vomiting and the CT finding of intracranial injury could be noted. Analyzed data have led to believe that GCS of 13 at presentation is the only important clinical predictor of intracranial injury. Conclusion: Retrospective data, small sample size and limited number of factors for assessing clinical manifestation might present constraints on the predictive rule that was derived from this review. Such limitations notwithstanding, the decision to determine which patients should undergo neuroimaging is encouraged to be based on clinical judgments. Further analysis with higher sample sizes may be required to authenticate and validate findings. PMID:25949038

  16. Brain metabolite abnormalities in ventromedial prefrontal cortex are related to duration of hypercortisolism and anxiety in patients with Cushing's syndrome.

    PubMed

    Crespo, Iris; Santos, Alicia; Gómez-Ansón, Beatriz; López-Mourelo, Olga; Pires, Patricia; Vives-Gilabert, Yolanda; Webb, Susan M; Resmini, Eugenia

    2016-09-01

    Chronic exposure to excessive glucocorticoid (GC) concentration in Cushing's syndrome (CS) can affect the brain structurally and functionally; ventromedial prefrontal cortex (vmPFC) is rich in GC receptors and therefore particularly vulnerable to excessive GC concentration. Proton magnetic resonance spectroscopy ((1)H-MRS) is a sensitive, non-invasive imaging technique that provides information on brain metabolites in vivo. Our aim was to investigate metabolite concentrations in vmPFC of CS patients and their relationship with clinical outcome. Twenty-two right-handed CS patients (7 active/15 in remission, 19 females, 41.6 ± 12.3 years) and 22 right-handed healthy controls (14 females, 41.7 ± 11 years) underwent brain MRI and (1)H-MRS exams at 3 Tesla. Concentrations of glutamate (Glu), glutamate + glutamine (Glx), creatine (Cr), N-Acetyl-aspartate (NAA), N-Acetyl-aspartate + N-acetylaspartylglutamate (total NAA), choline-containing compounds (Cho) and myoinositol (MI) were determined. Moreover, anxiety and depressive symptoms were evaluated with the State-Trait Anxiety Inventory (STAI) and the Beck Depression Inventory-II (BDI-II) test, respectively. CS patients had lower concentrations of glutamate and total NAA in the vmPFC than healthy controls (8.6 ± 1.2 vs. 9.3 ± 0.7 mmol/L, and 6.4 ± 0.8 vs. 6.8 ± 0.4 mmol/L, respectively; p < 0.05). Duration of hypercortisolism was negatively correlated with total NAA (r = -0.488, p < 0.05). Moreover, the concentration of total NAA was negatively correlated with anxiety state (r = -0.359, p < 0.05). Brain metabolites are abnormal in the vmPFC of patients with CS. Decreased total NAA and glutamate concentrations indicate neuronal dysfunction that appear to be related with duration of hypercortisolism and anxiety. PMID:27103571

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

    PubMed Central

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

    2013-01-01

    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 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), 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/sec. 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 2-parameter Mooney-Rivlin hyperelastic model and a viscoelastic model with a 2nd order prony series. Main results Estimated shear moduli using a 2nd order viscoelastic model increased from 0.5 - 2.6 kPa (day 1 of implantation) to 25.7 - 59.3 kPa (4 weeks of implantation) and subsequently decreased to 0.8 - 7.9 kPa after 6-8 weeks of implantation in 6 of 7 animals. Estimated elastic moduli increased from 4.1-7.8 kPa on the day of implantation to 24 - 44.9 kPa after 4 weeks. The elastic moduli was estimated to be 6.8-33.3 kPa in 6 of 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 moduli 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 induced stresses on the

  18. Optimal Gaussian Mixture Models of Tissue Intensities in Brain MRI of Patients with Multiple-Sclerosis

    NASA Astrophysics Data System (ADS)

    Xiao, Yiming; Shah, Mohak; Francis, Simon; Arnold, Douglas L.; Arbel, Tal; Collins, D. Louis

    Brain tissue segmentation is important in studying markers in human brain Magnetic Resonance Images (MRI) of patients with diseases such as Multiple Sclerosis (MS). Parametric segmentation approaches typically assume unimodal Gaussian distributions on MRI intensities of individual tissue classes, even in applications on multi-spectral images. However, this assumption has not been rigorously verified especially in the context of MS. In this work, we evaluate the local MRI intensities of both healthy and diseased brain tissues of 21 multi-spectral MRIs (63 volumes in total) of MS patients for adherence to this assumption. We show that the tissue intensities are not uniform across the brain and vary across (anatomical) regions of the brain. Consequently, we show that Gaussian mixtures can better model the multi-spectral intensities. We utilize an Expectation Maximization (EM) based approach to learn the models along with a symmetric Jeffreys divergence criterion to study differences in intensity distributions. The effects of these findings are also empirically verified on automatic segmentation of brains with MS.

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

    SciTech Connect

    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.

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

    PubMed

    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. PMID:22711258

  1. Impact of brain tissue filtering on neurostimulation fields: a modeling study

    PubMed Central

    Wagner, Tim; Eden, Uri; Rushmore, Jarrett; Russo, Christopher J.; Dipietro, Laura; Fregni, Felipe; Simon, Stephen; Rotman, Stephen; Pitskel, Naomi B.; Ramos-Estebanez, Ciro; Pascual-Leone, Alvaro; Grodzinsky, Alan J.; Zahn, Markus; Valero-Cabre, Antoni

    2013-01-01

    Electrical neurostimulation techniques, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), are increasingly used in the neurosciences, e.g., for studying brain function, and for neurotherapeutics, e.g., for treating depression, epilepsy, and Parkinson’s disease. The characterization of electrical properties of brain tissue has guided our fundamental understanding and application of these methods, from electrophysiologic theory to clinical dosing-metrics. Nonetheless, prior computational models have primarily relied on ex-vivo impedance measurements. We recorded the in-vivo impedances of brain tissues during neurosurgical procedures and used these results to construct MRI guided computational models of TMS and DBS neurostimulatory fields and conductance-based models of neurons exposed to stimulation. We demonstrated that tissues carry neurostimulation currents through frequency dependent resistive and capacitive properties not typically accounted for by past neurostimulation modeling work. We show that these fundamental brain tissue properties can have significant effects on the neurostimulatory-fields (capacitive and resistive current composition and spatial/temporal dynamics) and neural responses (stimulation threshold, ionic currents, and membrane dynamics). These findings highlight the importance of tissue impedance properties on neurostimulation and impact our understanding of the biological mechanisms and technological potential of neurostimulatory methods. PMID:23850466

  2. Estimation of contrast agent concentration in intra- and extra-vascular spaces of brain tissue.

    PubMed

    Yahaghi, E; Soltanian-Zadeh, H; Shahriari, M; Fatouraee, N; Ewing, J R

    2006-11-01

    This article presents a new method for estimating the leakage of a contrast agent out of a vessel. The proposed method is developed based on tissue homogeneity (TH) model, modified Patlak model, and Monte Carlo simulation. The analytical methods published in the literature estimate the contrast agent leakage by solving the coupled differential equations associated with the TH model under adiabatic conditions. These methods employ unrealistic simplifying assumptions and become intractable in their applications to the vessels that have a non-uniform permeability. Without making any unrealistic assumptions, our approach simply tracks the passage of the contrast agent through the capillary and its crossing of the vessel walls based on the blood flow in the vessel, the vessel's permeability, and the condition of the blood-brain barrier (BBB). These are treated as statistical processes that can be modeled reasonably well using the Monte Carlo method. In the proposed approach, the intra- and extra-vascular spaces are divided into multiple compartments, similar to the Patlak model. A real, measured arterial input function (AIF) is used as the capillary input and the concentration of the contrast agent is found as a function of time and distance, inside and outside of the capillary. This is done for normal and abnormal capillaries with uniform and non-uniform permeability. The proposed method generates concentration curves similar to those of the analytical method for simple AIF models. It also generates reasonable concentration curves for a real AIF. The proposed method does not fit a mathematical function to the measured AIF and does not make unrealistic simplifying assumptions. It is not therefore prone to the fitting errors and generates more realistic and more accurate results than the analytical methods. PMID:16978665

  3. Cutaneous Heterotopic Brain Tissue (Neuroglial Choristoma) with Dysplastic Features in a Kitten.

    PubMed

    Ramírez, G A; Ressel, L; Altimira, J; Vilafranca, M

    2016-07-01

    A 3-month-old, male European shorthair kitten exhibited an ill-defined, soft mass on the skin of the frontal head, which was present since birth. The surgically resected tissue was representative of a discrete dermal and subcutaneous mass comprising islands of neurons, glial and meningothelial elements, sometimes atypical or dysplastic, separated by dense collagenous connective tissue. There was no evident connection between this tissue and the brain. Immunohistochemical examination confirmed the presence of neurons and a pleocellular glial population, supporting a diagnosis of cutaneous neuroglial choristoma believed to be secondary to sequestered (resolved) meningoencephalocoele. Ectopic brain tissue is very rare in small animals. Some atypical features displayed by this tissue may be misdiagnosed as neoplasia. Communication between surgeon and pathologist to clarify the relationship of the lesion to surrounding structures is helpful to avoid misdiagnosis. PMID:27324745

  4. Differentiation of healthy brain tissue and tumors using surface-enhanced Raman scattering.

    PubMed

    Aydin, Omer; Altaş, Murat; Kahraman, Mehmet; Bayrak, Omer Faruk; Culha, Mustafa

    2009-10-01

    Surface-enhanced Raman scattering (SERS) is a powerful technique for characterization of biological samples. SERS spectra from healthy brain tissue and tumors are obtained by sudden freezing of tissue in liquid nitrogen and crashing and mixing it with a concentrated silver colloidal suspension. The acquired spectra from tissues show significant spectral differences that can be used to identify whether it is from a healthy region or tumor. The most significant change on SERS spectra from the healthy/peripheral brain tissue to tumor is the increase of the ratio of the peaks at around 723 to 655 cm(-1). In addition, the spectral changes indicate that the protein content in tumors increases compared to the peripheral/healthy tissue as observed with tumor invasion. The preliminary results show that SERS spectra can be used for a quick diagnosis due to the simplicity of the sample preparation and the speed of the spectral acquisition. PMID:19843358

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

    NASA Astrophysics Data System (ADS)

    Saiga, Rino; Mizutani, Ryuta; Inomoto, Chie; Takekoshi, Susumu; Nakamura, Naoya; Tsuboi, Akio; Osawa, Motoki; Arai, Makoto; Oshima, Kenichi; Itokawa, Masanari; Uesugi, Kentaro; Takeuchi, Akihisa; Terada, Yasuko; Suzuki, Yoshio

    2016-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

    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

  7. Removal of brain tissue by 1940-nm Tm-Fiber laser

    NASA Astrophysics Data System (ADS)

    Tunç, Burcu; Gülsoy, Murat

    2011-03-01

    The aim of the study was to investigate the thermal effects of the 1940-nm Tm-fiber laser on the dead brain tissue. 4-5 mm coronal sections were taken from lamb brains. Tm-fiber laser was applied at the back (cortical) and below the cortex (subcortical) of these slices with 0.5 mm distance. At the beginning of the research in order to find appropriate laser parameter to be compared for 1940-nm Tm-fiber laser, the carbonization and coagulation times of the brain slices were recorded for each power value, both for cortical and subcortical tissue. The appropriate laser parameters for lamb brain tissue were selected according to this study. Lasers were applied in both continuous and pulsed modes. In continuous mode, doses were changed with fixed application time. In pulsed mode, doses were modified with the change in pulse width. The lesions were detected with microscope. The radius of ablation and coagulation for each laser application was recorded. By calculating ablation efficiency (100xablation/calculation radius) the aproppriate laser doses were determined for both cortical and subcortical tissue. The maximum ablation efficiency for cortical tissue in continuous mode was 200 mW and 600 mW and in pulsed mode was 600 mW and for subcortical tissue maximum ablation efficiency was found 600 mW in both continuous mode and pulsed mode.

  8. Brain tissue volume changes in relapsing-remitting multiple sclerosis: correlation with lesion load.

    PubMed

    Quarantelli, Mario; Ciarmiello, Andrea; Morra, Vincenzo Brescia; Orefice, Giuseppe; Larobina, Michele; Lanzillo, Roberta; Schiavone, Vittorio; Salvatore, Elena; Alfano, Bruno; Brunetti, Arturo

    2003-02-01

    The aim of this study was to simultaneously measure in vivo volumes of gray matter (GM), normal white matter (WM), abnormal white matter (aWM), and cerebro-spinal fluid (CSF), and to assess their relationship in 50 patients with relapsing-remitting multiple sclerosis (RR-MS) (age range, 21-59; mean EDSS, 2.5; mean disease duration, 9.9 years), using an unsupervised multiparametric segmentation procedure applied to brain MR studies. Tissue volumes were normalized to total intracranial volume providing corresponding fractional volumes (fGM, faWM, fWM, and fCSF), subsequently corrected for aWM-related segmentation inaccuracies and adjusted to mean patients' age according to age-related changes measured in 54 normal volunteers (NV) (age range 16-70). In MS patients aWM was 23.8 +/- 29.8 ml (range 0.4-138.8). A significant decrease in fGM was present in MS patients as compared to NV (49.5 +/- 3.2% vs 53.3 +/- 2.1%; P < 0.0001), with a corresponding increase in fCSF (13.0 +/- 3.8% vs 9.1 +/- 2.4%; P < 0.0001). No difference could be detected between the two groups for fWM (37.5 +/- 2.6% vs 37.6 +/- 2.2%). faWM correlated inversely with fGM (R = -0.434, P < 0.001 at regression analysis), and directly with fCSF (R = 0.473, P < 0.001), but not with fWM. There was a significant correlation between disease duration and EDSS, while no relationship was found between EDSS or disease duration and fractional volumes. Brain atrophy in RR-MS is mainly related to GM loss, which correlates with faWM. Both measures do not appear to significantly affect EDSS, which correlates to disease duration. PMID:12595189

  9. The NSW brain tissue resource centre: Banking for alcohol and major neuropsychiatric disorders research.

    PubMed

    Sutherland, G T; Sheedy, D; Stevens, J; McCrossin, T; Smith, C C; van Roijen, M; Kril, J J

    2016-05-01

    The New South Wales Brain Tissue Resource Centre (NSWBTRC) at the University of Sydney (Australia) is an established human brain bank providing tissue to the neuroscience research community for investigations on alcohol-related brain damage and major psychiatric illnesses such as schizophrenia. The NSWBTRC relies on wide community engagement to encourage those with and without neuropsychiatric illness to consent to donation through its allied research programs. The subsequent provision of high-quality samples relies on standardized operational protocols, associated clinical data, quality control measures, integrated information systems, robust infrastructure, and governance. These processes are continually augmented to complement the changes in internal and external governance as well as the complexity and diversity of advanced investigation techniques. This report provides an overview of the dynamic process of brain banking and discusses the challenges of meeting the future needs of researchers, including synchronicity with other disease-focus collections. PMID:27139235

  10. Brain abnormalities in male children and adolescents with hemophilia: detection with MR imaging. The Hemophilia Growth and Development Study Group.

    PubMed

    Wilson, D A; Nelson, M D; Fenstermacher, M J; Bohan, T P; Hopper, K D; Tilton, A; Mitchell, W G; Contant, C F; Maeder, M A; Donfield, S M

    1992-11-01

    Cranial magnetic resonance (MR) imaging was performed in 124 male patients (aged 7-19 years), from 14 institutions, in whom a diagnosis of moderate to severe hemophilia was made. Blood tests in all subjects were negative for human immunodeficiency virus. Findings in MR studies were abnormal in 25 (20.2%) subjects. Six lesions in five subjects were classified as congenital. The most commonly identified congenital lesion was a posterior fossa collection of cerebrospinal fluid (five cases). Twenty-two subjects had acquired lesions that were probably related to the hemophilia or its treatment. The most commonly acquired lesions were single- or multifocal areas of high signal intensity within the white matter on T2-weighted images noted in 14 (11.3%) subjects. Two subjects had large focal areas of brain atrophy, and six had some degree of diffuse cerebral cortical atrophy. Three subjects (2.4%) had hemorrhagic lesions. To the authors' knowledge, the unexpected finding of small, focal, nonhemorrhagic white matter lesions has not previously been reported. PMID:1410372

  11. Tissue Non-specific Alkaline Phosphatase (TNAP) in Vessels of the Brain.

    PubMed

    Deracinois, Barbara; Lenfant, Anne-Marie; Dehouck, Marie-Pierre; Flahaut, Christophe

    2015-01-01

    The microvessels of the brain represent around 3-4 % of the brain compartment but constitute the most important length (400 miles) and surface of exchange (20 m(2)) between the blood and the parenchyma of brain. Under influence of surrounding tissues, the brain microvessel endothelium expresses a specific phenotype that regulates and restricts the entry of compounds and cells from blood to brain, and defined the so-called blood-brain barrier (BBB). Evidences that alkaline phosphatase (AP) is a characteristic feature of the BBB phenotype that allows differentiating capillary endothelial cells from brain to those of the periphery have rapidly emerge. Thenceforth, AP has been rapidly used as a biomarker of the blood-brain barrier phenotype. In fact, brain capillary endothelial cells (BCECs) express exclusively tissue non-specific alkaline phosphatase (TNAP). There are several lines of evidence in favour of an important role for TNAP in brain function. TNAP is thought to be responsible for the control of transport of some compounds across the plasma membrane of the BCECs. Here, we report that levamisole-mediated inhibition of TNAP provokes an increase of the permeability to Lucifer Yellow of the endothelial monolayer. Moreover, we illustrate the disruption of the cytoskeleton organization. Interestingly, all observed effects were reversible 24 h after levamisole removal and correlated with the return of a full activity of the TNAP. This reversible effect remains to be studied in details to evaluate the potentiality of a levamisole treatment to enhance the entry of drugs in the brain parenchyma. PMID:26219710

  12. Automated Brain Tissue Segmentation Based on Fractional Signal Mapping from Inversion Recovery Look-Locker Acquisition

    PubMed Central

    Shin, Wanyong; Geng, Xiujuan; Gu, Hong; Zhan, Wang; Zou, Qihong; Yang, Yihong

    2010-01-01

    Most current automated segmentation methods are performed on T1- or T2-weighted MR images, relying on relative image intensity that is dependent on other MR parameters and sensitive to B1 magnetic field inhomogeneity. Here, we propose an image segmentation method based on quantitative longitudinal magnetization relaxation time (T1) of brain tissues. Considering the partial volume effect, fractional volume maps of brain tissues (white matter, gray matter, and cerebrospinal fluid) were obtained by fitting the observed signal in an inversion recovery procedure to a linear combination of three exponential functions, which represents the relaxations of each of the tissue types. A Look-Locker acquisition was employed to accelerate the acquisition process. The feasibility and efficacy of this proposed method were evaluated using simulations and experiments. The potential applications of this method in the study of neurological disease as well as normal brain development and aging are discussed. PMID:20452444

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

    NASA Astrophysics Data System (ADS)

    Ide-Ektessabi, Ari; Ota, Yukihide; Ishihara, Ryoko; Mizuno, Yutaka; Takeuchi, Tohru

    2005-12-01

    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.

  14. Extraction, Identification, and Quantification of Histones from Small Quantities of Specific Brain Tissue.

    PubMed

    Beldjoud, Hassiba; Messanvi, Fany; Nadif Kasri, Nael; Roozendaal, Benno

    2016-01-01

    Histone posttranslational modifications (PTMs), by their action on the chromatin state, play a central role in the regulation of gene expression. The discovery that some PTMs in the brain are dynamically regulated by experience and environmental factors makes them an important subject for the study of plasticity changes in learning and memory, addiction, and psychiatric disorders. Current histone isolation protocols, however, require large amounts of tissue, which limits their application for analyzing small tissue samples from a specific brain region. We describe here a step-by-step protocol for histone extraction and isolation from 1 mm(3) of tissue from brain punches, which allows reproducible and reliable results for histone PTM identification and quantification without losing anatomical precision. © 2016 by John Wiley & Sons, Inc. PMID:27367963

  15. Preparation of mouse brain tissue for immunoelectron microscopy.

    PubMed

    Tremblay, Marie-Eve; Riad, Mustapha; Majewska, Ania

    2010-01-01

    Transmission electron microscopy (TEM) is extremely useful for visualizing microglial, oligodendrocytic, astrocytic, and neuronal subcellular compartments (dendrite, dendritic spine, axon, axon terminal, perikaryon), as well as their intracellular organelles and cytoskeleton, in the central nervous system at high spatial resolution. Combined with TEM, pre-embedding immunocytochemistry allows the discrimination of cellular elements with few distinctive features and identification criteria (e.g., microglial perikarya and processes, when using an antibody against the microglia-specific marker Iba1 (ionized calcium binding adaptor molecule 1; as presented here)), identifying the neurotransmitter contents of cellular elements (e.g., serotonergic) and their ultrastructural localization of soluble or membrane-bound proteins (e.g., 5 HT1A and EphA4 receptors). Here, we describe a protocol for transcardiac perfusion of mice with acrolein fixative, removal and sectioning of the brain, as well as immunoperoxidase-diaminobenzidine (DAB) staining, resin embedding, and ultrathin sectioning of the brain sections. Upon completion of these procedures, the immunostained material is ready for examination with TEM. When rigorously performed, this technique provides an excellent compromise between optimal ultrastructural preservation and immunocytochemical detection. PMID:20689505

  16. Are brain and heart tissue prone to the development of thiamine deficiency?

    PubMed

    Klooster, Astrid; Larkin, James R; Wiersema-Buist, Janneke; Gans, Reinold O B; Thornalley, Paul J; Navis, Gerjan; van Goor, Harry; Leuvenink, Henri G D; Bakker, Stephan J L

    2013-05-01

    Thiamine deficiency is a continuing problem leading to beriberi and Wernicke's encephalopathy. The symptoms of thiamine deficiency develop in the heart, brain and neuronal tissue. Yet, it is unclear how rapid thiamine deficiency develops and which organs are prone to development of thiamine deficiency. We investigated these issues in a thiamine deficient animal model. Twenty-four male Lewis rats were fed a thiamine deficient diet, which contained 0.04% of normal thiamine intake. Six control rats were fed 200 μg of thiamine per day. Every week a group of six rats on the thiamine-deficient diet was sacrificed and blood, urine and tissue were stored. Blood and tissue transketolase activity, thiamine and thiamine metabolites were measured and PCR of thiamine transporter-1 (ThTr-1) was performed. Transketolase activity was significantly reduced in red blood cells, liver, lung, kidney and spleen tissue after two weeks of thiamine deficient diet. In brain tissue, transketolase activity was not reduced after up to four weeks of thiamine deficient diet. The amount of thiamine pyrophosphate was also significantly conserved in brain and heart tissue (decrease of 31% and 28% respectively), compared to other tissues (decrease of ~70%) after four weeks of thiamine deficient diet. There was no difference between tissues in ThTr-1 expression after four weeks of thiamine deficient diet. Despite the fact that the heart and the brain are predilection sites for complications from thiamine deficiency, these tissues are protected against thiamine deficiency. Other organs could be suffering from thiamine deficiency without resulting in clinical signs of classic thiamine deficiency in beriberi and Wernicke's encephalopathy. PMID:23357554

  17. High-resolution x-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue

    SciTech Connect

    Collingwood, J.F.; Mikhaylova, A.; Davidson, M.R.; Batich, C.; Streit, W.J.; Eskin, T.; Terry, J.; Barrea, R.; Underhill, R.S.; Dobson, J.

    2008-06-16

    Fluorescence mapping and microfocus X-ray absorption spectroscopy are used to detect, locate and identify iron biominerals and other inorganic metal accumulations in neurodegenerative brain tissue at sub-cellular resolution (< 5 microns). Recent progress in developing the technique is reviewed. Synchrotron X-rays are used to map tissue sections for metals of interest, and XANES and XAFS are used to characterize anomalous concentrations of the metals in-situ so that they can be correlated with tissue structures and disease pathology. Iron anomalies associated with biogenic magnetite, ferritin and haemoglobin are located and identified in an avian tissue model with a pixel resolution {approx} 5 microns. Subsequent studies include brain tissue sections from transgenic Huntington's mice, and the first high-resolution mapping and identification of iron biominerals in human Alzheimer's and control autopsy brain tissue. Technical developments include use of microfocus diffraction to obtain structural information about biominerals in-situ, and depositing sample location grids by lithography for the location of anomalies by conventional microscopy. The combined techniques provide a breakthrough in the study of both intra- and extra-cellular iron compounds and related metals in tissue. The information to be gained from this approach has implications for future diagnosis and treatment of neurodegeneration, and for our understanding of the mechanisms involved.

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

    PubMed

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    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. PMID:27057543

  19. BDNF promoter I methylation correlates between post-mortem human peripheral and brain tissues.

    PubMed

    Stenz, Ludwig; Zewdie, Seblewongel; Laforge-Escarra, Térèse; Prados, Julien; La Harpe, Romano; Dayer, Alexandre; Paoloni-Giacobino, Ariane; Perroud, Nader; Aubry, Jean-Michel

    2015-02-01

    Several psychiatric disorders have been associated with CpG methylation changes in CG rich promoters of the brain-derived neurotrophic factor (BDNF) mainly by extracting DNA from peripheral blood cells. Whether changes in peripheral DNA methylation can be used as a proxy for brain-specific alterations remains an open question. In this study we aimed to compare DNA methylation levels in BDNF promoter regions in human blood cells, muscle and brain regions using bisulfite-pyrosequencing. We found a significant correlation between the levels of BDNF promoter I methylation measured in quadriceps and vPFC tissues extracted from the same individuals (n = 98, Pearson, r = 0.48, p = 4.5 × 10(-7)). In the hippocampus, BDNF promoter I and IV methylation levels were strongly correlated (Pearson, n = 37, r = 0.74, p = 1.4 × 10(-7)). We found evidence for sex-dependent effect on BDNF promoter methylation levels in the various tissues and blood samples. Taken together, these data indicate a strong intra-individual correlation between peripheral and brain tissue. They also suggest that sex determines methylation patterns in BDNF promoter region across different types of tissue, including muscle, brain, and blood. PMID:25450314

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

    PubMed Central

    Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

    2016-01-01

    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. PMID:27057543

  1. Brain banks: benefits, limitations and cautions concerning the use of post-mortem brain tissue for molecular studies.

    PubMed

    Ferrer, Isidre; Martinez, Anna; Boluda, Susana; Parchi, Piero; Barrachina, Marta

    2008-09-01

    Brain banks are facilities providing an interface between generous donation of nervous tissues and research laboratories devoted to increase our understanding of the diseases of the nervous system, discover new diagnostic targets, and develop new strategies. Considering this crucial role, it is important to learn about the suitabilities, limitations and proper handling of individual brain samples for particular studies. Several factors may interfere with preservation of DNA, RNA, proteins and lipids, and, therefore, special care must be taken first to detect sub-optimally preserved tissues and second to provide adequate material for each specific purpose. Basic aspects related with DNA, RNA and protein preservation include agonal state, post-mortem delay, temperature of storage and procedures of tissue preservation. Examination of DNA and RNA preservation is best done by using bioanalyzer technologies instead of less sensitive methods such as agarose gels. Adequate RNA preservation is mandatory in RNA microarray studies and adequate controls are necessary for proper PCR validation. Like for RNA, the preservation of proteins is not homogeneous since some molecules are more vulnerable than others. This aspect is crucial in the study of proteins including expression levels and possible post-translational modifications. Similarly, the reliability of functional and enzymatic studies in human post-mortem brain largely depends on protein preservation. Much less is known about other aspects, such as the effects of putative deleterious factors on epigenetic events such as methylation of CpGs in gene promoters, nucleosome preservation, histone modifications, and conservation of microRNA species. Most brains are appropriate for morphological approaches but not all brains are useful for certain biochemical and molecular studies. PMID:18543077

  2. Rheological regional properties of brain tissue studied under cyclic creep/ recovery shear stresses

    NASA Astrophysics Data System (ADS)

    Boudjema, F.; Lounis, M.; Khelidj, B.; Bessai, N.

    2015-04-01

    The rheological properties of brain tissue were studied by repeated creep-recovery shear tests under static conditions for different regions. Corpus callosum CC, Thalamus Th and Corona radiata CR. Non-linear viscoelastic model was also proposed to characterize the transient/steady states of shear creep results. From the creep-recovery data it was obvious that the brain tissues show high regional anisotropy. However. the both samples exhibit fluid viscoelastic properties in the first shear stress cycle of 100 Pa, while this behaviour evolutes to solid viscoelastic with cyclic effect.

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Detection of AIDS Virus in Macrophages in Brain Tissue from AIDS Patients with Encephalopathy

    NASA Astrophysics Data System (ADS)

    Koenig, Scott; Gendelman, Howard E.; Orenstein, Jan M.; Canto, Mauro C.; Pezeshkpour, Gholam H.; Yungbluth, Margaret; Janotta, Frank; Aksamit, Allen; Martin, Malcolm A.; Fauci, Anthony S.

    1986-09-01

    One of the common neurological complications in patients with the acquired immune deficiency syndrome (AIDS) is a subacute encephalopathy with progressive dementia. By using the techniques of cocultivation for virus isolation, in situ hybridization, immunocytochemistry, and transmission electron microscopy, the identity of an important cell type that supports replication of the AIDS retrovirus in brain tissue was determined in two affected individuals. These cells were mononucleated and multinucleated macrophages that actively synthesized viral RNA and produced progeny virions in the brains of the patients. Infected brain macrophages may serve as a reservoir for virus and as a vehicle for viral dissemination in the infected host.

  5. Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

    PubMed

    Ronsoni, Marcelo Fernando; Remor, Aline Pertile; Lopes, Mark William; Hohl, Alexandre; Troncoso, Iris H Z; Leal, Rodrigo Bainy; Boos, Gustavo Luchi; Kondageski, Charles; Nunes, Jean Costa; Linhares, Marcelo Neves; Lin, Kátia; Latini, Alexandra Susana; Walz, Roger

    2016-04-01

    Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery. PMID:26586405

  6. Infiltrating cells from host brain restore the microglial population in grafted cortical tissue.

    PubMed

    Wang, Cong; Tao, Sijue; Fang, Yukun; Guo, Jing; Zhu, Lirui; Zhang, Shengxiang

    2016-01-01

    Transplantation of embryonic cortical tissue is considered as a promising therapy for brain injury. Grafted neurons can reestablish neuronal network and improve cortical function of the host brain. Microglia is a key player in regulating neuronal survival and plasticity, but its activation and dynamics in grafted cortical tissue remain unknown. Using two-photon intravital imaging and parabiotic model, here we investigated the proliferation and source of microglia in the donor region by transplanting embryonic cortical tissue into adult cortex. Live imaging showed that the endogenous microglia of the grafted tissue were rapidly lost after transplantation. Instead, host-derived microglia infiltrated and colonized the graft. Parabiotic model suggested that the main source of infiltrating cells is the parenchyma of the host brain. Colonized microglia proliferated and experienced an extensive morphological transition and eventually differentiated into resting ramified morphology. Collectively, these results demonstrated that donor tissue has little contribution to the activated microglia and host brain controls the microglial population in the graft. PMID:27615195

  7. Profile analysis of hepatic porcine and murine brain tissue slices obtained with a vibratome.

    PubMed

    Mattei, G; Cristiani, I; Magliaro, C; Ahluwalia, A

    2015-01-01

    This study is aimed at characterizing soft tissue slices using a vibratome. In particular, the effect of two sectioning parameters (i.e., step size and sectioning speed) on resultant slice thickness was investigated for fresh porcine liver as well as for paraformaldehyde-fixed (PFA-fixed) and fresh murine brain. A simple framework for embedding, sectioning and imaging the slices was established to derive their thickness, which was evaluated through a purposely developed graphical user interface. Sectioning speed and step size had little effect on the thickness of fresh liver slices. Conversely, the thickness of PFA-fixed murine brain slices was found to be dependent on the step size, but not on the sectioning speed. In view of these results, fresh brain tissue was sliced varying the step size only, which was found to have a significant effect on resultant slice thickness. Although precision-cut slices (i.e., with regular thickness) were obtained for all the tissues, slice accuracy (defined as the match between the nominal step size chosen and the actual slice thickness obtained) was found to increase with tissue stiffness from fresh liver to PFA-fixed brain. This quantitative investigation can be very helpful for establishing the most suitable slicing setup for a given tissue. PMID:25945319

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

    PubMed Central

    Francik, Renata; Kryczyk, Jadwiga; Krośniak, Mirosław; Berköz, Mehmet; Sanocka, Ilona; Francik, Sławomir

    2014-01-01

    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. PMID:25401157

  9. Profile analysis of hepatic porcine and murine brain tissue slices obtained with a vibratome

    PubMed Central

    Mattei, G; Cristiani, I; Magliaro, C

    2015-01-01

    This study is aimed at characterizing soft tissue slices using a vibratome. In particular, the effect of two sectioning parameters (i.e., step size and sectioning speed) on resultant slice thickness was investigated for fresh porcine liver as well as for paraformaldehyde-fixed (PFA-fixed) and fresh murine brain. A simple framework for embedding, sectioning and imaging the slices was established to derive their thickness, which was evaluated through a purposely developed graphical user interface. Sectioning speed and step size had little effect on the thickness of fresh liver slices. Conversely, the thickness of PFA-fixed murine brain slices was found to be dependent on the step size, but not on the sectioning speed. In view of these results, fresh brain tissue was sliced varying the step size only, which was found to have a significant effect on resultant slice thickness. Although precision-cut slices (i.e., with regular thickness) were obtained for all the tissues, slice accuracy (defined as the match between the nominal step size chosen and the actual slice thickness obtained) was found to increase with tissue stiffness from fresh liver to PFA-fixed brain. This quantitative investigation can be very helpful for establishing the most suitable slicing setup for a given tissue. PMID:25945319

  10. A new use for long-term frozen brain tissue: Golgi impregnation

    PubMed Central

    Melendez-Ferro, Miguel; Perez-Costas, Emma; Roberts, Rosalinda C.

    2009-01-01

    The study of dendritic spine shape and number has become a standard in the analysis of synaptic transmission anomalies since a considerable number of neuropsychiatric and neurological diseases have their foundation in alterations in these structures. One of the best ways to study possible alterations of dendritic spines is the use of Golgi impregnation. Although usually the Golgi method implies the use of fresh or fixed tissue, here we report the use of Golgi-Cox for the staining of human and animal brain tissue kept frozen for long periods of time. We successfully applied the Golgi-Cox method to human brain tissue stored for up to 15 years in a freezer. The technique produced reliable and reproducible impregnation of dendrites and dendritic spines in different cortical areas. We also applied the same technique to rat brain frozen for up to one year, obtaining the same satisfactory results. The fact that Golgi-Cox can be successfully applied to this type of tissue adds a new value for hundreds of frozen human or animal brains kept in the freezers of the laboratories, that otherwise would not be useful for anything else. Researchers other than neuroanatomists, i.e. in fields such as biochemistry and molecular biology can also benefit from a simple and reliable technique that can be applied to tissue left from their primary experiments. PMID:18789970

  11. Cellular telephones and effects on the brain: the head as an antenna and brain tissue as a radio receiver.

    PubMed

    Weinberger, Z; Richter, E D

    2002-12-01

    Headache and other neuropsychological symptoms occur in users of cellular telephones, and controversy exists concerning risks for brain cancer. We hypothesize these effects result from the head serving as an antenna and brain tissue as a radio receiver. The frequencies for transmission and reception by cellular telephones, about 900 MHz for analog and 1800 MHz for digital transmission, have wavelengths of 33-35 and 16-17 cm, respectively. Human heads are oval in shape with a short axis about 16 to 17 cm in length. Near the ear there will be a cross-section in the head with an axis half the wavelength of RF/MW transmissions of 900 MHz and equal to the wavelength of RF/MW transmissions at 1800 MHz. Therefore, the human head can serve as a lossy resonator for the electromagnetic radiation emitted by the cellular telephone, absorbing much of the energy specifically from these wavelengths. Brain cells and tissues demodulate the cell-phone's audio frequencies from the radio frequency carrier. Low audio frequencies in the ranges of alpha and beta waves affect these waves and thereby influence brain function. These effects state the case for a precautionary policy. PMID:12445512

  12. 65zinc uptake from blood into brain and other tissues in the rat

    SciTech Connect

    Pullen, R.G.; Franklin, P.A.; Hall, G.H. )

    1990-10-01

    Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied 65Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to 65Zn in the anaesthetized rat in vivo. Adult male Wistar rats within the weight range 500-600 g were used. 65ZnCl2 and (125I)albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests 65Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times less than 30 min, 65Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for 65Zn of about 4 ml/100g which is not csf.

  13. Non-diffeomorphic registration of brain tumor images by simulating tissue loss and tumor growth.

    PubMed

    Zacharaki, Evangelia I; Hogea, Cosmina S; Shen, Dinggang; Biros, George; Davatzikos, Christos

    2009-07-01

    Although a variety of diffeomorphic deformable registration methods exist in the literature, application of these methods in the presence of space-occupying lesions is not straightforward. The motivation of this work is spatial normalization of MR images from patients with brain tumors in a common stereotaxic space, aiming to pool data from different patients into a common space in order to perform group analyses. Additionally, transfer of structural and functional information from neuroanatomical brain atlases into the individual patient's space can be achieved via the inverse mapping, for the purpose of segmenting brains and facilitating surgical or radiotherapy treatment planning. A method that estimates the brain tissue loss and replacement by tumor is applied for achieving equivalent image content between an atlas and a patient's scan, based on a biomechanical model of tumor growth. Automated estimation of the parameters modeling brain tissue loss and displacement is performed via optimization of an objective function reflecting feature-based similarity and elastic stretching energy, which is optimized in parallel via APPSPACK (Asynchronous Parallel Pattern Search). The results of the method, applied to 21 brain tumor patients, indicate that the registration accuracy is relatively high in areas around the tumor, as well as in the healthy portion of the brain. Also, the calculated deformation in the vicinity of the tumor is shown to correlate highly with expert-defined visual scores indicating the tumor mass effect, thereby potentially leading to an objective approach to quantification of mass effect, which is commonly used in diagnosis. PMID:19408350

  14. Brain tissue segmentation in 4D CT using voxel classification

    NASA Astrophysics Data System (ADS)

    van den Boom, R.; Oei, M. T. H.; Lafebre, S.; Oostveen, L. J.; Meijer, F. J. A.; Steens, S. C. A.; Prokop, M.; van Ginneken, B.; Manniesing, R.

    2012-02-01

    A method is proposed to segment anatomical regions of the brain from 4D computer tomography (CT) patient data. The method consists of a three step voxel classification scheme, each step focusing on structures that are increasingly difficult to segment. The first step classifies air and bone, the second step classifies vessels and the third step classifies white matter, gray matter and cerebrospinal fluid. As features the time averaged intensity value and the temporal intensity change value were used. In each step, a k-Nearest-Neighbor classifier was used to classify the voxels. Training data was obtained by placing regions of interest in reconstructed 3D image data. The method has been applied to ten 4D CT cerebral patient data. A leave-one-out experiment showed consistent and accurate segmentation results.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Diagnosis of osteomyelitis in the presence of soft-tissue infection and radiologic evidence of osseous abnormalities: Value of leukocyte scintigraphy

    SciTech Connect

    Jacobson, A.F.; Harley, J.D.; Lipsky, B.A.; Pecoraro, R.E. )

    1991-10-01

    To evaluate the usefulness of 111In-leukocyte scintigraphy for identifying osteomyelitis in the presence of soft-tissue infection, the author prospectively studied 45 bone sites adjacent to soft-tissue infection in patients with abnormal findings on radiographs and 99mTc bone scans that were suggestive of osteomyelitis. 111In-leukocyte scans were analyzed in terms of the intensity of abnormal uptake and its location relative to bone. The diagnosis of osteomyelitis was established from results of percutaneous bone biopsy culture (n = 35), histologic examination of surgical specimens (n = 8), and clinical follow-up (n = 2). Osteomyelitis was present at 22 sites, including 16 of 18 sites with increased leukocyte uptake in bone, resulting in a sensitivity of 73%, specificity of 91%, and positive predictive value of 89% for this finding. Osteomyelitis was present at four of 17 sites with predominantly soft-tissue localization of leukocyte activity in the region of bone, none of seven sites with normal leukocyte scans, and two of three sites with diminished leukocyte uptake in bone. Although not helpful in distinguishing infectious from noninfectious bone abnormalities, 3- and especially 24-hr bone scans viewed in conjunction with leukocyte studies provided important correlation to aid in estimating the location of focal abnormal leukocyte uptake. The finding of soft-tissue infection with increased uptake of labeled leukocytes that extends to involve adjacent bone strongly suggests concurrent osteomyelitis. When the presence of abnormal leukocyte uptake in bone is uncertain, additional imaging and possibly biopsy may be required to establish or exclude the diagnosis of osteomyelitis.

  17. Magnetic Resonance Microscopy at 14 Tesla and Correlative Histopathology of Human Brain Tumor Tissue

    PubMed Central

    Gonzalez-Segura, Ana; Morales, Jose Manuel; Gonzalez-Darder, Jose Manuel; Cardona-Marsal, Ramon; Lopez-Gines, Concepcion; Cerda-Nicolas, Miguel; Monleon, Daniel

    2011-01-01

    Magnetic Resonance Microscopy (MRM) can provide high microstructural detail in excised human lesions. Previous MRM images on some experimental models and a few human samples suggest the large potential of the technique. The aim of this study was the characterization of specific morphological features of human brain tumor samples by MRM and correlative histopathology. We performed MRM imaging and correlative histopathology in 19 meningioma and 11 glioma human brain tumor samples obtained at surgery. To our knowledge, this is the first MRM direct structural characterization of human brain tumor samples. MRM of brain tumor tissue provided images with 35 to 40 µm spatial resolution. The use of MRM to study human brain tumor samples provides new microstructural information on brain tumors for better classification and characterization. The correlation between MRM and histopathology images allowed the determination of image parameters for critical microstructures of the tumor, like collagen patterns, necrotic foci, calcifications and/or psammoma bodies, vascular distribution and hemorrhage among others. Therefore, MRM may help in interpreting the Clinical Magnetic Resonance images in terms of cell biology processes and tissue patterns. Finally, and most importantly for clinical diagnosis purposes, it provides three-dimensional information in intact samples which may help in selecting a preferential orientation for the histopathology slicing which contains most of the informative elements of the biopsy. Overall, the findings reported here provide a new and unique microstructural view of intact human brain tumor tissue. At this point, our approach and results allow the identification of specific tissue types and pathological features in unprocessed tumor samples. PMID:22110653

  18. Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

    PubMed

    Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

    2015-04-01

    Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. PMID:25616867

  19. Abnormal N-glycosylation pattern for brain nucleotide pyrophosphatase-5 (NPP-5) in Mecp2-mutant murine models of Rett syndrome.

    PubMed

    Cortelazzo, Alessio; De Felice, Claudio; Guerranti, Roberto; Signorini, Cinzia; Leoncini, Silvia; Pecorelli, Alessandra; Scalabrì, Francesco; Madonna, Michele; Filosa, Stefania; Della Giovampaola, Cinzia; Capone, Antonietta; Durand, Thierry; Mirasole, Cristiana; Zolla, Lello; Valacchi, Giuseppe; Ciccoli, Lucia; Guy, Jacky; D'Esposito, Maurizio; Hayek, Joussef

    2016-04-01

    Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methyl-CpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. PMID:26476268

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

    NASA Astrophysics Data System (ADS)

    Anand, S.; Cicchi, R.; Giordano, F.; Buccoliero, A. M.; Guerrini, R.; Pavone, F. S.

    2014-12-01

    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.

  1. Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development

    PubMed Central

    Girardi, G; Fraser, J; Lennen, R; Vontell, R; Jansen, M; Hutchison, G

    2015-01-01

    In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration in the mouse model of APS and in the PTB model. In the APS model, foetuses that showed increased C3 in their brains additionally expressed anxiety-related behaviour after birth. Importantly, USPIO did not affect pregnancy outcomes and liver function in the mother and the offspring, suggesting that this method may be useful for detecting complement activation in vivo in utero and predicting placental insufficiency and abnormal foetal neurodevelopment that leads to neuropsychiatric disorders. PMID:25245499

  2. Optical properties of mouse brain tissue after optical clearing with FocusClear™

    NASA Astrophysics Data System (ADS)

    Moy, Austin J.; Capulong, Bernard V.; Saager, Rolf B.; Wiersma, Matthew P.; Lo, Patrick C.; Durkin, Anthony J.; Choi, Bernard

    2015-09-01

    Fluorescence microscopy is commonly used to investigate disease progression in biological tissues. Biological tissues, however, are strongly scattering in the visible wavelengths, limiting the application of fluorescence microscopy to superficial (<200 μm) regions. Optical clearing, which involves incubation of the tissue in a chemical bath, reduces the optical scattering in tissue, resulting in increased tissue transparency and optical imaging depth. The goal of this study was to determine the time- and wavelength-resolved dynamics of the optical scattering properties of rodent brain after optical clearing with FocusClear™. Light transmittance and reflectance of 1-mm mouse brain sections were measured using an integrating sphere before and after optical clearing and the inverse adding doubling algorithm used to determine tissue optical scattering. The degree of optical clearing was quantified by calculating the optical clearing potential (OCP), and the effects of differing OCP were demonstrated using the optical histology method, which combines tissue optical clearing with optical imaging to visualize the microvasculature. We observed increased tissue transparency with longer optical clearing time and an analogous increase in OCP. Furthermore, OCP did not vary substantially between 400 and 1000 nm for increasing optical clearing durations, suggesting that optical histology can improve ex vivo visualization of several fluorescent probes.

  3. Neuroimaging of schizophrenia: structural abnormalities and pathophysiological implications

    PubMed Central

    Buckley, Peter F

    2005-01-01

    Schizophrenia, once considered a psychological malady devoid of any organic brain substrate, has been the focus of intense neuroimaging research. Findings reveal mild but generalized tissue loss as well as more selective focal loss. It is unclear whether these abnormalities reflect neurodevelopmental or neurodegenerative processes, or some combination of each; current evidence favors a preponderance of neurodevelopmental abnormalities. The pattern of brain abnormalities is also influenced by environmental and genetic risk factors, as well as by the course (and possibly even treatment) of this illness. These findings are described in this article. PMID:18568069

  4. Mercury speciation in brain tissue of polar bears (Ursus maritimus) from the Canadian Arctic.

    PubMed

    Krey, Anke; Kwan, Michael; Chan, Hing Man

    2012-04-01

    Methylmercury (MeHg) is a neurotoxicant that has been found at elevated concentrations in the Arctic ecosystem. Little is known about its internal dose in wildlife such as polar bears. We measured concentrations of mercury (Hg) in three different brain regions (cerebellum, frontal lobe and brain stem) of 24 polar bears collected from the Nunavik, Canada between 2000 and 2003. Speciation of Hg was measured by High Performance Liquid Chromatography coupled to Inductively Coupled Plasma Mass Spectroscopy (HPLC-ICP-MS). Concentrations of mean total Hg in brain tissue were up to 625 times lower (0.28 ± 0.07 mg kg(-1) dry weight (dw) in frontal lobe, 0.23 ± 0.07 mg kg(-1) dw in cerebellum and 0.12 ± 0.0 3mg kg(-1) dw in brain stem) than the mean total Hg concentration previously reported in polar bear liver collected from Eastern Baffin Island. Methylmercury (MeHg) accounted for 100% of the Hg found in all three brain regions analyzed. These results suggest that polar bear might reduce the toxic effects of Hg by limiting the uptake into the brain and/or decrease the rate of demethylation so that Hg can be excreted from the brain more easily. The toxicokinetics and the blood-brain-barrier mechanisms of polar bears are still unknown and further research is required. PMID:22406289

  5. Early Social Enrichment Rescues Adult Behavioral and Brain Abnormalities in a Mouse Model of Fragile X Syndrome

    PubMed Central

    Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

    2015-01-01

    Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases. PMID:25348604

  6. Diazepam binding inhibitor gene expression: Location in brain and peripheral tissues of rate

    SciTech Connect

    Alho, H.; Fremeau, R.T. Jr.; Tiedge, H.; Wilcox, J.; Bovolin, P.; Brosius, J.; Roberts, J.L.; Costa, E.

    1988-09-01

    Diazepam binding inhibitor (DBI), an endogenous 10-kDa polypeptide was isolated from rat and human brain by monitoring displacement of radioactive diazepam bound to specific recognition sites in brain synaptic and mitochondrial membranes. The cellular location of DBI mRNA was studied in rat brain and selected peripheral tissues by in situ hybridization histochemistry with a /sup 35/S-labeled single-stranded complementary RNA probe. DBI mRNA was heterogeneously distributed in rat brain, with particularly high levels in the area postrema, the cerebellar cortex, and ependyma of the third ventricle. Intermediate levels were found in the olfactory bulb, pontine nuclei, inferior colliculi, arcuate nucleus, and pineal gland. Relatively low but significant levels of silver grains were observed overlying many mesencephalic and telencephalic areas that have previously been shown to contain numerous DBI-immunoreactive neurons and a high density of central benzodiazepine receptors. In situ hybridizations also revealed high levels of DBI mRNA in the posterior lobe of the pituitary gland, liver, and germinal center of the white pulp of spleen, all tissues that are rich in peripheral benzodiazepine binding sites. The tissue-specific pattern of DBI gene expression described here could be exploited to further understand the physiological function of DBI in the brain and periphery.

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Multimodality Instrument for Tissue Characterization

    NASA Technical Reports Server (NTRS)

    Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

    2000-01-01

    A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip is discussed. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network, program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration.

  9. Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

    PubMed

    El Chehadeh, Salima; Faivre, Laurence; Mosca-Boidron, Anne-Laure; Malan, Valérie; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Callier, Patrick; Lefebvre, Mathilde; Marle, Nathalie; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Le Caignec, Cédric; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Goldenberg, Alice; Cormier-Daire, Valérie; Rio, Marlène; Bonnefont, Jean-Paul; Thevenon, Julien; Echenne, Bernard; Journel, Hubert; Afenjar, Alexandra; Burglen, Lydie; Bienvenu, Thierry; Addor, Marie-Claude; Lebon, Sébastien; Martinet, Danièle; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Devillard, Françoise; Coutton, Charles; Lacombe, Didier; Delrue, Marie-Ange; Philip, Nicole; Moncla, Anne; Badens, Catherine; Perreton, Nathalie; Masurel, Alice; Thauvin-Robinet, Christel; Des Portes, Vincent; Guibaud, Laurent

    2016-01-01

    Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment. PMID:26420639

  10. Autonomous control for mechanically stable navigation of microscale implants in brain tissue to record neural activity.

    PubMed

    Anand, Sindhu; Kumar, Swathy Sampath; Muthuswamy, Jit

    2016-08-01

    Emerging neural prosthetics require precise positional tuning and stable interfaces with single neurons for optimal function over a lifetime. In this study, we report an autonomous control to precisely navigate microscale electrodes in soft, viscoelastic brain tissue without visual feedback. The autonomous control optimizes signal-to-noise ratio (SNR) of single neuronal recordings in viscoelastic brain tissue while maintaining quasi-static mechanical stress conditions to improve stability of the implant-tissue interface. Force-displacement curves from microelectrodes in in vivo rodent experiments are used to estimate viscoelastic parameters of the brain. Using a combination of computational models and experiments, we determined an optimal movement for the microelectrodes with bidirectional displacements of 3:2 ratio between forward and backward displacements and a inter-movement interval of 40 s for minimizing mechanical stress in the surrounding brain tissue. A regulator with the above optimal bidirectional motion for the microelectrodes in in vivo experiments resulted in significant reduction in the number of microelectrode movements (0.23 movements/min) and longer periods of stable SNR (53 % of the time) compared to a regulator using a conventional linear, unidirectional microelectrode movement (with 1.48 movements/min and stable SNR 23 % of the time). PMID:27457752

  11. CALCIUM ION EFFLUX INDUCTION IN BRAIN TISSUE BY RADIO-FREQUENCY RADIATION

    EPA Science Inventory

    One of the most interesting and controversial papers on the biological effects of nonionizing radiation was published by Bawin, Kaczmarek and Adey in 1975. They found a 147 MHz carrier wave could elicit and enhance efflux of calcium ions from chick brain tissue only when amplitud...

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

    PubMed Central

    Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    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. PMID:25894337

  13. Brain tissue deforms similarly to filled elastomers and follows consolidation theory

    NASA Astrophysics Data System (ADS)

    Franceschini, G.; Bigoni, D.; Regitnig, P.; Holzapfel, G. A.

    2006-12-01

    Slow, large deformations of human brain tissue—accompanying cranial vault deformation induced by positional plagiocephaly, occurring during hydrocephalus, and in the convolutional development—has surprisingly received scarce mechanical investigation. Since the effects of these deformations may be important, we performed a systematic series of in vitro experiments on human brain tissue, revealing the following features. (i) Under uniaxial (quasi-static), cyclic loading, brain tissue exhibits a peculiar nonlinear mechanical behaviour, exhibiting hysteresis, Mullins effect and residual strain, qualitatively similar to that observed in filled elastomers. As a consequence, the loading and unloading uniaxial curves have been found to follow the Ogden nonlinear elastic theory of rubber (and its variants to include Mullins effect and permanent strain). (ii) Loaded up to failure, the "shape" of the stress/strain curve qualitatively changes, evidencing softening related to local failure. (iii) Uniaxial (quasi-static) strain experiments under controlled drainage conditions provide the first direct evidence that the tissue obeys consolidation theory involving fluid migration, with properties similar to fine soils, but having much smaller volumetric compressibility. (iv) Our experimental findings also support the existence of a viscous component of the solid phase deformation. Brain tissue should, therefore, be modelled as a porous, fluid-saturated, nonlinear solid with very small volumetric (drained) compressibility.

  14. OFF-CENTER SPHERICAL MODEL FOR DOSIMETRY CALCULATIONS IN CHICK BRAIN TISSUE

    EPA Science Inventory

    The paper presents calculations for the electric field and absorbed power density distribution in chick brain tissue inside a test tube, using an off-center spherical model. It is shown that the off-center spherical model overcomes many of the limitations of the concentric spheri...

  15. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

    PubMed

    Jugé, Lauriane; Pong, Alice C; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  16. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

    PubMed Central

    Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

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

    SciTech Connect

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

    1999-06-10

    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 degree sign 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.

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

    PubMed

    Polanco, Michael; Bawab, Sebastian; Yoon, Hargsoon

    2016-01-01

    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. PMID:27322338

  19. Methylenetetrahydrofolate reductase deficiency alters levels of glutamate and γ-aminobutyric acid in brain tissue

    PubMed Central

    Jadavji, N.M.; Wieske, F.; Dirnagl, U.; Winter, C.

    2015-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is an enzyme key regulator in folate metabolism. Deficiencies in MTHFR result in increased levels of homocysteine, which leads to reduced levels of S-adenosylmethionine (SAM). In the brain, SAM donates methyl groups to catechol-O-methyltransferase (COMT), which is involved in neurotransmitter analysis. Using the MTHFR-deficient mouse model the purpose of this study was to investigate levels of monoamine neurotransmitters and amino acid levels in brain tissue. MTHFR deficiency affected levels of both glutamate and γ-aminobutyric acid in within the cerebellum and hippocampus. Mthfr−/− mice had reduced levels of glutamate in the amygdala and γ-aminobutyric acid in the thalamus. The excitatory mechanisms of homocysteine through activation of the N-methyl-d-aspartate receptor in brain tissue might alter levels of glutamate and γ-aminobutyric acid. PMID:26937386

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

    PubMed Central

    Polanco, Michael; Bawab, Sebastian; Yoon, Hargsoon

    2016-01-01

    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. PMID:27322338

  1. Joining microelectronics and microionics: Nerve cells and brain tissue on semiconductor chips

    NASA Astrophysics Data System (ADS)

    Fromherz, Peter

    2008-09-01

    The direct electrical interfacing of semiconductor chips with individual nerve cells and with brain tissue is considered. At first, the structure of the cell-chip contact is described and then the electrical coupling is characterized between ion channels, the electrical elements of nerve cells, and transistors and capacitors of silicon chips. On that basis, the signal transmission between microelectronics and microionics is implemented in both directions. Simple hybrid systems are assembled with neuron pairs and with small neuronal networks. Finally, the interfacing with capacitors and transistors is extended to brain tissue on silicon. The application of CMOS chips with capacitively coupled recording sites allows an imaging of neuronal activity with high spatiotemporal resolution. Goal of the work is an integration of neuronal network dynamics and digital electronics on a microscopic level for applications in brain research, medical prosthetics and information technology.

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

    PubMed

    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. PMID:27062510

  3. Effects of tissue preservation temperature on high strain-rate material properties of brain.

    PubMed

    Zhang, Jiangyue; Yoganandan, Narayan; Pintar, Frank A; Guan, Yabo; Shender, Barry; Paskoff, Glenn; Laud, Purushottam

    2011-02-01

    Postmortem preservation conditions may be one of factors contributing to wide material property variations in brain tissues in literature. The objective of present study was to determine the effects of preservation temperatures on high strain-rate material properties of brain tissues using the split Hopkinson pressure bar (SHPB). Porcine brains were harvested immediately after sacrifice, sliced into 2 mm thickness, preserved in ice cold (group A, 10 samples) and 37°C (group B, 9 samples) saline solution and warmed to 37°C just prior to the test. A SHPB with tube aluminum transmission bar and semi-conductor strain gauges were used to enhance transmitted wave signals. Data were gathered using a digital acquisition system and processed to obtain stress-strain curves. All tests were conducted within 4 h postmortem. The mean strain-rate was 2487±72 s(-1). A repeated measures model with specimen-level random effects was used to analyze log transformed stress-strain responses through the entire loading range. The mean stress-strain curves with ±95% confidence bands demonstrated typical power relationships with the power value of 2.4519 (standard error, 0.0436) for group A and 2.2657 (standard error, 0.0443) for group B, indicating that responses for the two groups are significantly different. Stresses and tangent moduli rose with increasing strain levels in both groups. These findings indicate that storage temperatures affected brain tissue material properties and preserving tissues at 37°C produced a stiffer response at high strain-rates. Therefore, it is necessary to incorporate material properties obtained from appropriately preserved tissues to accurately predict the responses of brain using stress analyses models, such as finite element simulations. PMID:21055756

  4. Fitted hyperelastic parameters for Human brain tissue from reported tension, compression, and shear tests.

    PubMed

    Moran, Richard; Smith, Joshua H; García, José J

    2014-11-28

    The mechanical properties of human brain tissue are the subject of interest because of their use in understanding brain trauma and in developing therapeutic treatments and procedures. To represent the behavior of the tissue, we have developed hyperelastic mechanical models whose parameters are fitted in accordance with experimental test results. However, most studies available in the literature have fitted parameters with data of a single type of loading, such as tension, compression, or shear. Recently, Jin et al. (Journal of Biomechanics 46:2795-2801, 2013) reported data from ex vivo tests of human brain tissue under tension, compression, and shear loading using four strain rates and four different brain regions. However, they do not report parameters of energy functions that can be readily used in finite element simulations. To represent the tissue behavior for the quasi-static loading conditions, we aimed to determine the best fit of the hyperelastic parameters of the hyperfoam, Ogden, and polynomial strain energy functions available in ABAQUS for the low strain rate data, while simultaneously considering all three loading modes. We used an optimization process conducted in MATLAB, calling iteratively three finite element models developed in ABAQUS that represent the three loadings. Results showed a relatively good fit to experimental data in all loading modes using two terms in the energy functions. Values for the shear modulus obtained in this analysis (897-1653Pa) are in the range of those presented in other studies. These energy-function parameters can be used in brain tissue simulations using finite element models. PMID:25446271

  5. An analytical model for nanoparticles concentration resulting from infusion into poroelastic brain tissue.

    PubMed

    Pizzichelli, G; Di Michele, F; Sinibaldi, E

    2016-02-01

    We consider the infusion of a diluted suspension of nanoparticles (NPs) into poroelastic brain tissue, in view of relevant biomedical applications such as intratumoral thermotherapy. Indeed, the high impact of the related pathologies motivates the development of advanced therapeutic approaches, whose design also benefits from theoretical models. This study provides an analytical expression for the time-dependent NPs concentration during the infusion into poroelastic brain tissue, which also accounts for particle binding onto cells (by recalling relevant results from the colloid filtration theory). Our model is computationally inexpensive and, compared to fully numerical approaches, permits to explicitly elucidate the role of the involved physical aspects (tissue poroelasticity, infusion parameters, NPs physico-chemical properties, NP-tissue interactions underlying binding). We also present illustrative results based on parameters taken from the literature, by considering clinically relevant ranges for the infusion parameters. Moreover, we thoroughly assess the model working assumptions besides discussing its limitations. While not laying any claims of generality, our model can be used to support the development of more ambitious numerical approaches, towards the preliminary design of novel therapies based on NPs infusion into brain tissue. PMID:26656677

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

    NASA Astrophysics Data System (ADS)

    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.

  7. A Device for Long-Term Perfusion, Imaging, and Electrical Interfacing of Brain Tissue In vitro

    PubMed Central

    Killian, Nathaniel J.; Vernekar, Varadraj N.; Potter, Steve M.; Vukasinovic, Jelena

    2016-01-01

    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 toward 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. PMID:27065793

  8. Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue

    SciTech Connect

    Gallant,M.; Rak, M.; Szeghalmi, A.; Del Bigio, M.; Westaway, D.; Yang, J.; Julian, R.; Gough, K.

    2006-01-01

    The creatine/phosphocreatine system, regulated by creatine kinase, plays an important role in maintaining energy balance in the brain. Energy metabolism and the function of creatine kinase are known to be affected in Alzheimer diseased brain and in cells exposed to the {beta}-amyloid peptide. We used infrared microspectroscopy to examine hippocampal, cortical, and caudal tissue from 21-89-week-old transgenic mice expressing doubly mutant (K670N/M671L and V717F) amyloid precursor protein and displaying robust pathology from an early age. Microcrystalline deposits of creatine, suggestive of perturbed energetic status, were detected by infrared microspectroscopy in all animals with advanced plaque pathology. Relatively large creatine deposits were also found in hippocampal sections from post-mortem Alzheimer diseased human brain, compared with hippocampus from non-demented brain. We therefore speculate that this molecule is a marker of the disease process.

  9. Detection, identification and mapping of iron anomalies in brain tissue using X-ray absorption spectroscopy

    SciTech Connect

    Mikhaylova, A.; Davidson, M.; Toastmann, H.; Channell, J.E.T.; Guyodo, Y.; Batich, C.; Dobson, J.

    2008-06-16

    This work describes a novel method for the detection, identification and mapping of anomalous iron compounds in mammalian brain tissue using X-ray absorption spectroscopy. We have located and identified individual iron anomalies in an avian tissue model associated with ferritin, biogenic magnetite and haemoglobin with a pixel resolution of less than 5 {micro}m. This technique represents a breakthrough in the study of both intra- and extra-cellular iron compounds in brain tissue. The potential for high-resolution iron mapping using microfocused X-ray beams has direct application to investigations of the location and structural form of iron compounds associated with human neurodegenerative disorders - a problem which has vexed researchers for 50 years.

  10. Impact of wavefront distortion and scattering on 2-photon microscopy in mammalian brain tissue

    PubMed Central

    Chaigneau, Emmanuelle; Wright, Amanda J.; Poland, Simon P.; Girkin, John M.; Silver, R. Angus

    2011-01-01

    Two-photon (2P) microscopy is widely used in neuroscience, but the optical properties of brain tissue are poorly understood. We have investigated the effect of brain tissue on the 2P point spread function (PSF2P) by imaging fluorescent beads through living cortical slices. By combining this with measurements of the mean free path of the excitation light, adaptive optics and vector-based modeling that includes phase modulation and scattering, we show that tissue-induced wavefront distortions are the main determinant of enlargement and distortion of the PSF2P at intermediate imaging depths. Furthermore, they generate surrounding lobes that contain more than half of the 2P excitation. These effects reduce the resolution of fine structures and contrast and they, together with scattering, limit 2P excitation. Our results disentangle the contributions of scattering and wavefront distortion in shaping the cortical PSF2P, thereby providing a basis for improved 2P microscopy. PMID:22109156

  11. Detection, identification and mapping of iron anomalies in brain tissue using X-ray absorption spectroscopy

    PubMed Central

    Mikhaylova, A; Davidson, M; Toastmann, H; Channell, J.E.T; Guyodo, Y; Batich, C; Dobson, J

    2005-01-01

    This work describes a novel method for the detection, identification and mapping of anomalous iron compounds in mammalian brain tissue using X-ray absorption spectroscopy. We have located and identified individual iron anomalies in an avian tissue model associated with ferritin, biogenic magnetite and haemoglobin with a pixel resolution of less than 5 μm. This technique represents a breakthrough in the study of both intra- and extra-cellular iron compounds in brain tissue. The potential for high-resolution iron mapping using microfocused X-ray beams has direct application to investigations of the location and structural form of iron compounds associated with human neurodegenerative disorders—a problem which has vexed researchers for 50 years. PMID:16849161

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

    NASA Astrophysics Data System (ADS)

    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.

  13. A Simplified Workflow for Protein Quantitation of Rat Brain Tissues Using Label-Free Proteomics and Spectral Counting.

    PubMed

    Boutté, Angela M; Grant, Shonnette F; Dave, Jitendra R

    2016-01-01

    Mass spectrometry-based proteomics is an increasingly valuable tool for determining relative or quantitative protein abundance in brain tissues. A plethora of technical and analytical methods are available, but straightforward and practical approaches are often needed to facilitate reproducibility. This aspect is particularly important as an increasing number of studies focus on models of traumatic brain injury or brain trauma, for which brain tissue proteomes have not yet been fully described. This text provides suggested techniques for robust identification and quantitation of brain proteins by using molecular weight fractionation prior to mass spectrometry-based proteomics. Detailed sample preparation and generalized protocols for chromatography, mass spectrometry, spectral counting, and normalization are described. The rat cerebral cortex isolated from a model of blast-overpressure was used as an exemplary source of brain tissue. However, these techniques may be adapted for lysates generated from several types of cells or tissues and adapted by the end user. PMID:27604744

  14. Mechanical characterization of brain tissue in simple shear at dynamic strain rates.

    PubMed

    Rashid, Badar; Destrade, Michel; Gilchrist, Michael D

    2013-12-01

    During severe impact conditions, brain tissue experiences a rapid and complex deformation, which can be seen as a mixture of compression, tension and shear. Diffuse axonal injury (DAI) occurs in animals and humans when both the strains and strain rates exceed 10% and 10/s, respectively. Knowing the mechanical properties of brain tissue in shear at these strains and strain rates is thus of particular importance, as they can be used in finite element simulations to predict the occurrence of brain injuries under different impact conditions. However, very few studies in the literature provide this information. In this research, an experimental setup was developed to perform simple shear tests on porcine brain tissue at strain rates ≤120/s. The maximum measured shear stress at strain rates of 30, 60, 90 and 120/s was 1.15±0.25kPa, 1.34±0.19kPa, 2.19±0.225kPa and 2.52±0.27kPa, (mean±SD), respectively at the maximum amount of shear, K=1. Good agreement of experimental, theoretical (Ogden and Mooney-Rivlin models) and numerical shear stresses was achieved (p=0.7866-0.9935). Specimen thickness effects (2.0-10.0mm thick specimens) were also analyzed numerically and we found that there is no significant difference (p=0.9954) in the shear stress magnitudes, indicating a homogeneous deformation of the specimens during simple shear tests. Stress relaxation tests in simple shear were also conducted at different strain magnitudes (10-60% strain) with the average rise time of 14ms. This allowed us to estimate elastic and viscoelastic parameters (initial shear modulus, μ=4942.0Pa, and Prony parameters: g1=0.520, g2=0.3057, τ1=0.0264s, and τ2=0.011s) that can be used in FE software to analyze the non-linear viscoelastic behavior of brain tissue. This study provides new insight into the behavior in finite shear of brain tissue under dynamic impact conditions, which will assist in developing effective brain injury criteria and adopting efficient countermeasures against

  15. Mapping drug distribution in brain tissue using liquid extraction surface analysis mass spectrometry imaging.

    PubMed

    Swales, John G; Tucker, James W; Spreadborough, Michael J; Iverson, Suzanne L; Clench, Malcolm R; Webborn, Peter J H; Goodwin, Richard J A

    2015-10-01

    Liquid extraction surface analysis mass spectrometry (LESA-MS) is a surface sampling technique that incorporates liquid extraction from the surface of tissue sections with nanoelectrospray mass spectrometry. Traditional tissue analysis techniques usually require homogenization of the sample prior to analysis via high-performance liquid chromatography mass spectrometry (HPLC-MS), but an intrinsic weakness of this is a loss of all spatial information and the inability of the technique to distinguish between actual tissue penetration and response caused by residual blood contamination. LESA-MS, in contrast, has the ability to spatially resolve drug distributions and has historically been used to profile discrete spots on the surface of tissue sections. Here, we use the technique as a mass spectrometry imaging (MSI) tool, extracting points at 1 mm spatial resolution across tissue sections to build an image of xenobiotic and endogenous compound distribution to assess drug blood-brain barrier penetration into brain tissue. A selection of penetrant and "nonpenetrant" drugs were dosed to rats via oral and intravenous administration. Whole brains were snap-frozen at necropsy and were subsequently sectioned prior to analysis by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and LESA-MSI. MALDI-MSI, as expected, was shown to effectively map the distribution of brain penetrative compounds but lacked sufficient sensitivity when compounds were marginally penetrative. LESA-MSI was used to effectively map the distribution of these poorly penetrative compounds, highlighting its value as a complementary technique to MALDI-MSI. The technique also showed benefits when compared to traditional homogenization, particularly for drugs that were considered nonpenetrant by homogenization but were shown to have a measurable penetration using LESA-MSI. PMID:26350423

  16. The viral theory of schizophrenia revisited: Abnormal placental gene expression and structural changes with lack of evidence of H1N1 viral presence in placentae of infected mice or brains of exposed offspring

    PubMed Central

    Fatemi, S. Hossein; Folsom, Timothy D.; Rooney, Robert J.; Mori, Susumu; Kornfield, Tess E.; Reutiman, Teri J.; Kneeland, Rachel E.; Liesch, Stephanie B.; Hua, Kegang; Hsu, John; Patel, Divyen H.

    2011-01-01

    , and autism. Placentas from infected mice showed a number of morphological abnormalities including presence of thrombi and increased presence of immune cells. Additionally, we searched for presence of H1N1 viral-specific genes for M1/M2, NA, and NS1 in placentas of infected mice and brains of exposed offspring and found none. Our results demonstrate that prenatal viral infection disrupts structure and gene expression of the placenta, hippocampus, and prefrontal cortex potentially explaining deleterious effects in the exposed offspring without evidence for presence of viral RNAs in the target tissues. PMID:21277874

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Dynamic effects of point source electroporation on the rat brain tissue.

    PubMed

    Sharabi, Shirley; Last, David; Guez, David; Daniels, Dianne; Hjouj, Mohammad Ibrahim; Salomon, Sharona; Maor, Elad; Mardor, Yael

    2014-10-01

    In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, p<0.001) and the number of treatment pulses (r(2)=0.94, p<0.002). Blood-brain barrier disruption depicted 3.2±0.3 times larger volumes than the final permanent damage volumes (p<0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors. PMID:24976141

  19. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  20. Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

    PubMed

    Saucier-Sawyer, Jennifer K; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J; Zhang, Junwei; Quijano, Elias; Saltzman, W Mark

    2015-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One NP produced significantly higher brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects. PMID:26453169

  1. Systemic Delivery of Blood-Brain Barrier Targeted Polymeric Nanoparticles Enhances Delivery to Brain Tissue

    PubMed Central

    Saucier-Sawyer, Jennifer K.; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J.; Zhang, Junwei; Quijano, Elias; Saltzman, W. Mark

    2016-01-01

    Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer nanoparticle systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All nanoparticle preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One nanoparticle produced significantly higher brain uptake (~0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad nanoparticles provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing nanoparticle transport across the BBB does not necessarily yield proportional pharmacological effects. PMID:26453169

  2. Abnormal brain function of the rat neonate in a prenatal 5-bromo-2'-deoxyuridine (BrdU)-induced developmental disorder model.

    PubMed

    Ogawa, Tetsuo; Kuwagata, Makiko; Muneoka, Katsumasa; Wakai, Chizu; Senuma, Mika; Kubo, Hiroko; Shioda, Seiji

    2012-10-01

    Neonatal brain function was investigated in a prenatal BrdU-induced developmental disorder model, which has been reported to exhibit behavioral abnormalities such as locomotor hyperactivity, impaired learning and memory, and lower anxiety in offspring. After 1h home cage deprivation we observed an increase in the number of c-Fos (neuronal activity marker) immunoreactive cells in several brain regions of the olfactory and stress-related areas in normal neonates at 11 days. Next, pregnant rats were exposed to 50mg/kg of BrdU from gestation days 9-15, and their offspring at 11 days were home-cage deprived. Compared to vehicle control, the number of c-Fos immunoreactive cells in BrdU group was found to be decreased in the piriform cortex and locus coeruleus, which are known to play an important role in neonatal learning and memory. We also analyzed Pearson product-moment correlation coefficient of the number of c-Fos immunoreactive cells, focusing on the piriform cortex and locus coeruleus versus numerous other brain areas (11 areas including amygdala). Numerous significant correlations were observed in the vehicle control group, however, correlations of the locus coeruleus disappeared in the BrdU group. By observing c-Fos immunoreactivity after home cage deprivation our study uncovers abnormal brain functions as early as postnatal day 11 in this disorder model. Based on these results, we propose a new histological approach for functional characterization of developmental disorder models. PMID:22609825

  3. In vivo penetration mechanics and mechanical properties of mouse brain tissue at micrometer scales.

    PubMed

    Sharp, Andrew A; Ortega, Alicia M; Restrepo, Diego; Curran-Everett, Douglas; Gall, Ken

    2009-01-01

    Substantial advancement in the understanding of the neuronal basis of behavior and the treatment of neurological disorders has been achieved via the implantation of various devices into the brain. To design and optimize the next generation of neuronal implants while striving to minimize tissue damage, it is necessary to understand the mechanics of probe insertion at relevant length scales. Unfortunately, a broad-based understanding of brain-implant interactions at the necessary micrometer scales is largely missing. This paper presents a generalizable description of the micrometer-scale penetration mechanics and material properties of mouse brain tissue in vivo. Cylindrical stainless steel probes were inserted into the cerebral cortex and olfactory bulb of mice. The effects of probe size, probe geometry, insertion rate, insertion location, animal age, and the presence of the dura and pia on the resulting forces were measured continuously throughout probe insertion and removal. Material properties (modulus, cutting force, and frictional force) were extracted using mechanical analysis. The use of rigid, incompressible, cylindrical probes allows for a general understanding of how probe design and insertion methods influence the penetration mechanics of brain tissue in vivo that can be applied to the quantitative design of most future implantable devices. PMID:19224718

  4. The average baboon brain: MRI templates and tissue probability maps from 89 individuals.

    PubMed

    Love, Scott A; Marie, Damien; Roth, Muriel; Lacoste, Romain; Nazarian, Bruno; Bertello, Alice; Coulon, Olivier; Anton, Jean-Luc; Meguerditchian, Adrien

    2016-05-15

    The baboon (Papio) brain is a remarkable model for investigating the brain. The current work aimed at creating a population-average baboon (Papio anubis) brain template and its left/right hemisphere symmetric version from a large sample of T1-weighted magnetic resonance images collected from 89 individuals. Averaging the prior probability maps output during the segmentation of each individual also produced the first baboon brain tissue probability maps for gray matter, white matter and cerebrospinal fluid. The templates and the tissue probability maps were created using state-of-the-art, freely available software tools and are being made freely and publicly available: http://www.nitrc.org/projects/haiko89/ or http://lpc.univ-amu.fr/spip.php?article589. It is hoped that these images will aid neuroimaging research of the baboon by, for example, providing a modern, high quality normalization target and accompanying standardized coordinate system as well as probabilistic priors that can be used during tissue segmentation. PMID:26975558

  5. Evidence for Fungal Infection in Cerebrospinal Fluid and Brain Tissue from Patients with Amyotrophic Lateral Sclerosis

    PubMed Central

    Alonso, Ruth; Pisa, Diana; Marina, Ana Isabel; Morato, Esperanza; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients. PMID:25892962

  6. Colorization and Automated Segmentation of Human T2 MR Brain Images for Characterization of Soft Tissues

    PubMed Central

    Attique, Muhammad; Gilanie, Ghulam; Hafeez-Ullah; Mehmood, Malik S.; Naweed, Muhammad S.; Ikram, Masroor; Kamran, Javed A.; Vitkin, Alex

    2012-01-01

    Characterization of tissues like brain by using magnetic resonance (MR) images and colorization of the gray scale image has been reported in the literature, along with the advantages and drawbacks. Here, we present two independent methods; (i) a novel colorization method to underscore the variability in brain MR images, indicative of the underlying physical density of bio tissue, (ii) a segmentation method (both hard and soft segmentation) to characterize gray brain MR images. The segmented images are then transformed into color using the above-mentioned colorization method, yielding promising results for manual tracing. Our color transformation incorporates the voxel classification by matching the luminance of voxels of the source MR image and provided color image by measuring the distance between them. The segmentation method is based on single-phase clustering for 2D and 3D image segmentation with a new auto centroid selection method, which divides the image into three distinct regions (gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical knowledge). Results have been successfully validated on human T2-weighted (T2) brain MR images. The proposed method can be potentially applied to gray-scale images from other imaging modalities, in bringing out additional diagnostic tissue information contained in the colorized image processing approach as described. PMID:22479421

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

    NASA Astrophysics Data System (ADS)

    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.

  8. Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity

    PubMed Central

    Giles, James A; Greenhalgh, Andrew D; Davies, Claire L; Denes, Adam; Shaw, Tovah; Coutts, Graham; Rothwell, Nancy J; McColl, Barry W; Allan, Stuart M

    2015-01-01

    The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders. PMID:25367678

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

    PubMed Central

    Dewailly, E; Mulvad, G; Pedersen, H S; Ayotte, P; Demers, A; Weber, J P; Hansen, J C

    1999-01-01

    Organochlorines are persistent lipophilic compounds that accumulate in Inuit people living in circumpolar countries. Organochlorines accumulate as a result of the Inuits' large consumption of sea mammal fat; however, available data are limited to blood lipids, milk fat, and adipose tissue. We 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 than those measured using the same analytical method in samples from Canadians in Quebec City, Quebec. Brain lipids contained lower concentrations of all organochlorines than lipids extracted from other tissues. Organochlorine residue levels in lipid extracts from liver, omental fat, and subcutaneous abdominal fat samples were similar, with the exception of ss-hexachlorocyclohexane, which reached a greater concentration in liver lipids than in lipids from both adipose tissues (4-fold; p < 0. 05). Comparisons with available international data on adipose tissue levels reveal that the organochlorine body burden in the Inuit population of Greenland is presently among the highest resulting from environmental exposure. Images Figure 1 PMID:10504150

  10. Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

    NASA Astrophysics Data System (ADS)

    Ersen, Ali; Elkabes, Stella; Freedman, David S.; Sahin, Mesut

    2015-02-01

    Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

  11. Light microscopic localization of brain opiate receptors: a general autoradiographic method which preserves tissue quality

    SciTech Connect

    Herkenham, M.; Pert, C.B.

    1982-08-01

    A general technique is described for using slide-mounted unfixed tissue sections to characterize and visualize drug and neurotransmitter receptors in brain or other tissues. The preparation of material, from fresh frozen, unfixed brain to dried sections securely attached to slides, is described in detail. The tissue can be kept intact during incubation at varying temperatures in solutions containing radiolabeled ligand, ions, buffers, and allosteric effectors. Strategies are described for determining optimal stereospecific binding with highest signal-to-noise ratios and for determining that a meaningful receptor is being studied. Dry formaldehyde fixation by vapors from heated paraformaldehyde preserves the tissue quality and traps the ligand near its site on the receptor, permitting subsequent histological processing through alcohols, solvents, and aqueous media, including liquid nuclear track emulsion. Visualization of (/sup 3/H)naloxone- or (/sup 3/H)enkephalin-labeled opiate receptor distributions in rat and human brains is achieved by tritium-sensitive film or by classical wet emulsion autoradiography. The advantages of the film include its ease of use and the ability to quantify receptor density by densitometry which can be computer-assisted. The advantage of the emulsion is the greater resolution and the concomitant appearance of morphology in cell-stained sections. Examples of correlations of opiate receptor distributions which underlying cytoarchitecture illustrate the potential for receptor localization studies.

  12. Development of hyaluronic acid-based scaffolds for brain tissue engineering.

    PubMed

    Wang, Tzu-Wei; Spector, Myron

    2009-09-01

    Three-dimensional biodegradable porous scaffolds play vital roles in tissue engineering. In this study, a hyaluronic acid-collagen (HA-Coll) sponge with an open porous structure and mechanical behavior comparable to brain tissue was developed. HA-Coll scaffolds with different mixing ratios were prepared by a freeze-drying technique and crosslinked with water-soluble carbodiimide to improve mechanical stability. The pore structure of the samples was evaluated by light and scanning electron microscopy, and the mechanical behavior was analyzed by mechanical compression and tension testing. The degree of crosslinking was determined by the water absorption and trinitrobenzene sulfonic assay, and the HA content was determined by a carbazole assay. The results showed that HA-Coll scaffolds containing an open porous structure with a homogeneous pore size distribution could be fabricated. Certain features of the mechanical properties of HA-Coll scaffolds prepared with a Coll:HA mixing ratio of 1:2, and pure HA sponges, were comparable with brain tissue. Neural stem cells (NSCs) were expanded in number in monolayer culture and then seeded onto the three-dimensional scaffolds in order to investigate the effects of the different types of scaffolds on neurogenic induction of the cells. This study contributes to the understanding of the effects of HA content and crosslink treatment on pore characteristics, and mechanical behavior essential for the design of HA-Coll scaffolds suitable for NSC growth and differentiation for brain tissue engineering. PMID:19403351

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

    SciTech Connect

    Weaver, John; Yang, Yirong; Purvis, Rebecca; Weatherwax, Theodore; Rosen, Gerald M.; Liu, Ke Jian

    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

  14. Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre.

    PubMed

    Harper, Clive; Dixon, Gavin; Sheedy, Donna; Garrick, Therese

    2003-09-01

    Alcohol dependence and abuse are among the most costly health problems in the world from both social and economic points of view. Patterns of drinking appear to be changing throughout the world with more women and young people drinking heavily. Excessive drinking can lead to impairment of cognitive function and structural brain changes--some permanent, some reversible. Patterns of damage appear to relate to lifetime alcohol consumption but, more importantly, to associated medical complications. The most significant of these is the alcohol-related vitamin deficient state, the Wernicke-Korsakoff syndrome (WKS), which is caused by thiamin deficiency but is seen most commonly in alcoholics. Careful selection and classification of alcoholic cases into those with and without these complications, together with detailed quantitative neuropathological analyses has provided data that gives clues to the most vulnerable regions and cells in the brain. Brain shrinkage is largely accounted for by loss of white matter. Some of this damage appears to be reversible. Alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex (superior frontal association cortex), hypothalamus and cerebellum. No change is found in basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of these regions which are normal in uncomplicated alcoholics are damaged in those with the WKS. Dendritic and synaptic changes have been documented in alcoholics and these, together with receptor and transmitter changes, may explain functional changes and cognitive deficits, which precede more severe structural neuronal changes. A resource to provide human brain tissues for these types of studies has been developed at the University of Sydney--the New South Wales Tissue Resource Centre. The aim of this facility is to provide research groups throughout the world with fresh and/or frozen tissues from well-characterized cases of alcohol-related brain damage and matched

  15. Measuring cell-type specific differential methylation in human brain tissue.

    PubMed

    Montaño, Carolina M; Irizarry, Rafael A; Kaufmann, Walter E; Talbot, Konrad; Gur, Raquel E; Feinberg, Andrew P; Taub, Margaret A

    2013-01-01

    The behavior of epigenetic mechanisms in the brain is obscured by tissue heterogeneity and disease-related histological changes. Not accounting for these confounders leads to biased results. We develop a statistical methodology that estimates and adjusts for celltype composition by decomposing neuronal and non-neuronal differential signal. This method provides a conceptual framework for deconvolving heterogeneous epigenetic data from postmortem brain studies. We apply it to find cell-specific differentially methylated regions between prefrontal cortex and hippocampus. We demonstrate the utility of the method on both Infinium 450k and CHARM data. PMID:24000956

  16. Normal-appearing brain tissue analysis in radiologically isolated syndrome using 3 T MRI.

    PubMed

    Labiano-Fontcuberta, Andrés; Mato-Abad, Virginia; Álvarez-Linera, Juan; Hernández-Tamames, Juan Antonio; Martínez-Ginés, María Luisa; Aladro, Yolanda; Ayuso, Lucía; Domingo-Santos, Ángela; Benito-León, Julián

    2016-07-01

    To date, it remains largely unknown whether there is in radiologically isolated syndrome (RIS) brain damage beyond visible T2 white matter lesions. We used single- voxel proton magnetic resonance spectroscopy and diffusion tensor imaging (3 T MRI) to analyze normal-appearing brain tissue regions in 18 RIS patients and 18 matched healthy controls. T2-hyperintense lesion volumes and structural brain volumes were also measured. The absolute metabolite concentrations and ratios of total N-acetylaspartate+N-acetylaspartyl glutamate (NAA), choline-containing compounds, myoinositol, and glutamine-glutamate complex to creatine were calculated. Spectral analysis was performed by LCModel. Voxelwise morphometry analysis was performed to localize regions of brain tissue showing significant changes of fractional anisotropy or mean diffusivity. Compared with healthy controls, RIS patients did not show any significant differences in either the absolute concentration of NAA or NAA/Cr ratio in mid-parietal gray matter. A trend toward lower NAA concentrations (-3.35%) was observed among RIS patients with high risk for conversion to multiple sclerosis. No differences in the other metabolites or their ratios were observed. RIS patients showed lower fractional anisotropy only in clusters overlapping lesional areas, namely in the cingulate gyrus bilaterally and the frontal lobe subgyral bilaterally (P < 0.001). Normalized brain and cortical volumes were significantly lower in RIS patients than in controls (P = 0.01 and P = 0.03, respectively). Our results suggest that in RIS, global brain and cortical atrophy are not primarily driven by significant occult microstructural normal appearing brain damage. Longitudinal MRI studies are needed to better understand the pathological processes underlying this novel entity. PMID:27399108

  17. Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

    PubMed Central

    Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

    2015-01-01

    Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters. PMID:26495031

  18. Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child.

    PubMed

    Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

    2015-01-01

    Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters. PMID:26495031

  19. Segmentation of tumor and edema along with healthy tissues of brain using wavelets and neural networks.

    PubMed

    Demirhan, Ayşe; Toru, Mustafa; Guler, Inan

    2015-07-01

    Robust brain magnetic resonance (MR) segmentation algorithms are critical to analyze tissues and diagnose tumor and edema in a quantitative way. In this study, we present a new tissue segmentation algorithm that segments brain MR images into tumor, edema, white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF). The detection of the healthy tissues is performed simultaneously with the diseased tissues because examining the change caused by the spread of tumor and edema on healthy tissues is very important for treatment planning. We used T1, T2, and FLAIR MR images of 20 subjects suffering from glial tumor. We developed an algorithm for stripping the skull before the segmentation process. The segmentation is performed using self-organizing map (SOM) that is trained with unsupervised learning algorithm and fine-tuned with learning vector quantization (LVQ). Unlike other studies, we developed an algorithm for clustering the SOM instead of using an additional network. Input feature vector is constructed with the features obtained from stationary wavelet transform (SWT) coefficients. The results showed that average dice similarity indexes are 91% for WM, 87% for GM, 96% for CSF, 61% for tumor, and 77% for edema. PMID:25265636

  20. Dielectric properties of brain tissue between 0.01 and 10 GHz.

    PubMed

    Foster, K R; Schepps, J L; Stoy, R D; Schwan, H P

    1979-11-01

    Dielectric permittivity and conductivity are reported for grey and white matter from dog brain tissue between 0.01 and 10 GHz. Between 0.01 and approximately 1 GHz, the permittivity decreases and conductivity increases as a power law of frequency. Above 1 GHz, the conductivity increases quadratically with frequency due to dipolar reorientation of free water molecules in tissue; the apparent rotational relaxation frequency at 37 degrees C is 21--25 GHz, slightly below the 25 GHz characteristic frequency of pure water at that temperature. The microwave data are analysed using the Maxwell mixture theory applicable for a suspension of nonconducting, low permittivity spheres in bulk water. From the increase in conductivity above 1 GHz, and the tissue permittivity at 2--4 GHz, the apparent volume fraction of water is approximately 0.70 and 0.55 for grey and white matter, respectively, about 10--15% lower than respective values from the literature. This discrepancy is apparently due to a small fraction of water which does not contribute to the tissue permittivity above 1 GHz. Empirical equations are given to summarise the dielectric properties of 'average' brain tissue at 37 degrees C for future theoretical studies of microwave absorption in the head. PMID:531093

  1. Brain tissue oxygen, carbon dioxide, and pH in neurosurgical patients at risk for ischemia.

    PubMed

    Hoffman, W E; Charbel, F T; Edelman, G

    1996-03-01

    A sensor that measures oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH was evaluated in brain tissue of patients at risk for ischemia. The sensor is 0.5 mm in diameter and was inserted into cortex tissue in 14 patients undergoing craniotomy for cerebrovascular surgery. A compromised cerebral circulation was identified in 8 of 14 patients by single photon emission computed tomography (SPECT) scan, cerebral angiography, and transient ischemic episodes before surgery. Under baseline conditions with isoflurane anesthesia and normal blood gases, tissue P02 was lower in the eight compromised compared to six noncompromised patients (noncompromised 37 +/- 12 mm Hg, compromised 10 +/- 5 mm Hg; P < 0.05), PCO2 was increased (noncompromised 49 +/- 5 mm Hg, compromised 72 +/- 23 mm Hg; P < 0.05), and pH was decreased (noncompromised 7.16 +/- 0.08, compromised 6.82 +/- 0.21; P < 0.05). Critical tissue values for the identification of ischemia were a P02 of 20 mm Hg, PCO2 of 60 mm Hg, and a pH of 7.0. These results suggest that brain tissue measures of P02, PCO2, and pH provide information on the adequacy of cerebral perfusion in neurosurgical patients. PMID:8623965

  2. Gradient-based Magnetic Resonance Electrical Properties Imaging of Brain Tissues

    PubMed Central

    Liu, Jiaen; Zhang, Xiaotong; Schmitter, Sebastian; Van de Moortele, Pierre-Francois; He, Bin

    2015-01-01

    Electrical properties tomography (EPT) holds promise for noninvasively mapping at high spatial resolution the electrical conductivity and permittivity of biological tissues in vivo using a magnetic resonance imaging (MRI) scanner. In the present study, we developed a novel gradient-based EPT approach with greatly improved tissue boundary reconstruction and largely elevated robustness against measurement noise compared to existing techniques. Using a 7 Tesla MRI system, we report high-quality in vivo human brain electrical property images with refined structural details, which can potentially merit clinical diagnosis (such as cancer detection) and high-field MRI applications (local SAR quantification) in the future. PMID:25571378

  3. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair.

    PubMed

    Zhang, Zhen-Qiang; Song, Jun-Ying; Jia, Ya-Quan; Zhang, Yun-Ke

    2016-03-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury. PMID:27127482

  4. Changes of amino acid gradients in brain tissues induced by microwave irradiation and other means

    SciTech Connect

    Baxter, C.F.; Parsons, J.E.; Oh, C.C.; Wasterlain, C.G.; Baldwin, R.A. )

    1989-09-01

    Focused microwave irradiation to the head (FMI) has been used extensively by neurochemists for rapid inactivation of enzymatic activity in brain tissues and the preservation, for in vitro analysis, of in vivo substrate concentrations. Periodically the suitability of this technique for regional studies has been questioned. Evidence has now been obtained, on the basis of altered concentration gradients for GABA and taurine from the Substantia Nigra (SN) to an Adjacent Dorsal Area (ADJ), that FMI not only inactivates enzymes, but also facilitates rapid diffusion of small molecules from areas of high concentrations to adjacent areas of lower concentration. To a lesser extent, the implantation of plastic injection cannulas also decreased these concentration gradients. These results offer clear evidence that FMI is ill suited and unreliable for studies designed to map and compare the in vivo regional concentrations of diffusible organic molecules (such as amino acids) in brain tissues. Any invasive technique that compromises membrane barriers is likely to produce smaller similar effects.

  5. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair

    PubMed Central

    Zhang, Zhen-qiang; Song, Jun-ying; Jia, Ya-quan; Zhang, Yun-ke

    2016-01-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury. PMID:27127482

  6. Open lung ventilation in neurosurgery: an update on brain tissue oxygenation.

    PubMed

    Wolf, S; Plev, D V; Trost, H A; Lumenta, C B

    2005-01-01

    Recently, we showed the feasibility of ventilating neurosurgical patients with acute intracranial pathology and concomitant acute respiratory distress syndrome (ARDS) according the so-called Open Lung approach. This technique consists of low tidal volume, elevated positive expiratory pressure (PEEP) level and initial recruitment maneuvers to open up collapsed alveoli. In this report, we focus on our experience to guide recruitment with brain tissue oxygenation (pbrO2) probes. We studied recruitment maneuvers in thirteen patients with ARDS and acute brain injury such as subarachnoid hemorrhage and traumatic brain injury. A pbrO2 probe was implanted in brain tissue at risk for hypoxia. Recruitment maneuvers were performed at an inspired oxygen frcation (FiO2) of 1.0 and a PEEP level of 30 40 cmH2O for 40 seconds. The mean FiO2 necessary for normoxemia could be decreased from 0.85 +/- 0.17 before recruitment to 0.55 +/- 0.12 after 24 hours, while mean PbrO2 (24.6 mmHg before recruitment) did not change. At a mean of 17 minutes after the first recruitment maneuver, PbrO2 showed peak a value of 35.6 +/- 16.6 mmHg, reflecting improvement in arterial oxygenation at an FiO2 of 1.0. Brain tissue oxygenation monitoring provides a useful adjunct to estimate the effects of recruitment maneuvers and ventilator settings in neurosurgical patients with acute lung injury. PMID:16463830

  7. Brain tissue interaction with three-dimensional, honeycomb polycaprolactone-based scaffolds designed for cranial reconstruction following traumatic brain injury.

    PubMed

    Choy, David Kim Seng; Nga, Vincent Diong Weng; Lim, Jing; Lu, Jia; Chou, Ning; Yeo, Tseng Tsai; Teoh, Swee-Hin

    2013-11-01

    Following traumatic brain injury (TBI), resultant voids are unable to support injections of suspension treatments, leading to ineffective healing. Moreover, without a structure to support the large defect, the defect site suffers from mechanical instability, which may impair the healing process. Therefore, having a delivery vehicle that can temporarily fill and provide mechanical support to the defect site may alleviate the healing process. In this work, we reported for the first time, the inflammatory response of brain tissue with polycaprolactone (PCL) and PCL-tricalcium phosphate (TCP) scaffolds designed and fabricated for cranial reconstruction. After cranial defects were created in Sprague-Dawley rats, PCL and PCL-TCP scaffolds were implanted for a period of 1 week and 1 month. Following histology and immunofluorescence staining with the ionized calcium binding adaptor molecule-1 (IBA-1), glial fibrillary acidic protein (GFAP), nestin, and neuronal nuclei (NeuN), results indicated that IBA-1-positive activated microglia were observed across all groups, and declined significantly by 1 month (p<0.05). Interestingly, IBA-1-positive microglia were significantly fewer in the PCL-TCP group (p<0.05), suggesting a relatively milder inflammatory response. A decrease in the number of GFAP-positive cells among all groups over time (>29%) was also observed. Initially, astrocyte hypertrophy was observed proximal to the TBI site (55% in PCL and PCL-TCP groups, 75% in control groups), but it subsided by 1 month. Proximal to the TBI site, nestin immunoreactivity was intense during week 1, and which reduced by 1 month across all groups. NeuN-positive neurons were shrunken proximal to the TBI site (<0.9 mm), 32% smaller in the PCL-TCP group and 27% smaller in the PCL group. Based on above data indicating the comparatively milder, initial inflammatory response of brain tissue to PCL-TCP scaffolds, it is suggested that PCL-TCP scaffolds have notable clinical advantages as

  8. The brain tissue response to surgical injury and its possible contribution to glioma recurrence.

    PubMed

    Hamard, Lauriane; Ratel, David; Selek, Laurent; Berger, François; van der Sanden, Boudewijn; Wion, Didier

    2016-05-01

    Surgery is the first line therapy for glioma. However, glioma recurs in 90 % of the patients in the resection margin. The impact of surgical brain injury (SBI) on glioma recurrence is largely overlooked. Herein, we review some of the mechanisms involved in tissue repair that may impact glioma recurrence at the resection margin. Many processes or molecules involved in tissue repair after brain injury are also critical for glioma growth. They include a wide array of secreted growth factors, cytokines and transcription factors including NFКB and STAT3 which in turn activate proliferative and anti-apoptotic genes and processes such as angiogenesis and inflammation. Because some residual glioma cells always remain in the tumor resection margin, there are now compelling arguments to suggest that some aspects of the brain tissue response to SBI can also participate to glioma recurrence at the resection margin. Brain tissue response to SBI recruits angiogenesis and inflammation that precede and then follow tumor recurrence at the resection margin. The healing response to SBI is double edged, as inflammation is involved in regeneration and healing, and has both pro- and anti-tumorigenic functions. A promising therapeutic approach is to normalize and re-educate the molecular and cellular responses at the resection margin to promote anti-tumorigenic processes involved in healing while inhibiting pro-tumorigenic activities. Manipulation of the inflammatory response to SBI to prevent local recurrence could also enhance the efficacy of other therapies such as immunotherapy. However, our current knowledge is far from sufficient to achieve this goal. Acknowledging, understanding and manipulating the double-edged role played by SBI in glioma recurrence is surely challenging, but it cannot be longer delayed. PMID:26961772

  9. Validation of partial tissue segmentation of single-channel magnetic resonance images of the brain.

    PubMed

    Grabowski, T J; Frank, R J; Szumski, N R; Brown, C K; Damasio, H

    2000-12-01

    We describe and evaluate a practical, automated algorithm based on local statistical mixture modeling for segmenting single-channel, T1-weighted volumetric magnetic resonance images of the brain into gray matter, white matter, and cerebrospinal fluid. We employed a stereological sampling method to assess, prospectively, the performance of the method with respect to human experts on 10 normal T1-weighted brain scans acquired with a three-dimensional gradient echo pulse sequence. The overall kappa statistic for the concordance of the algorithm with the human experts was 0.806, while that among raters, excluding the algorithm, was 0.802. The algorithm had better agreement with the modal expert decision (kappa = 0.878). The algorithm could not be distinguished from the experts by this measure. We also validated the algorithm on a simulated MR scan of a digital brain phantom with known tissue composition. Global gray matter and white matter errors were 1% and <1%, respectively, and correlation coefficients with the underlying tissue model were 0.95 for gray matter, 0.98 for white matter, and 0.95 for cerebrospinal fluid. In both approaches to validation, we evaluated both local and global performance of the algorithm. Human experts generated slightly higher global gray matter proportion estimates on the test brain scans relative to the algorithm (3.7%) and on the simulated MR scan relative to the true tissue model (4.4%). The algorithm underestimated gray in some subcortical nuclei which contain admixed gray and white matter. We demonstrate the reliability of the method on individual 1 NEX data sets of the test subjects, and its insensitivity to the precise values of initial model parameters. The output of this algorithm is suitable for quantifying cerebral cortical tissue, using a commonly performed commercial pulse sequence. PMID:11112396

  10. Lack of Evidence for Regional Brain Volume or Cortical Thickness Abnormalities in Youths at Clinical High Risk for Psychosis: Findings From the Longitudinal Youth at Risk Study.

    PubMed

    Klauser, Paul; Zhou, Juan; Lim, Joseph K W; Poh, Joann S; Zheng, Hui; Tng, Han Ying; Krishnan, Ranga; Lee, Jimmy; Keefe, Richard S E; Adcock, R Alison; Wood, Stephen J; Fornito, Alex; Chee, Michael W L

    2015-11-01

    There is cumulative evidence that young people in an "at-risk mental state" (ARMS) for psychosis show structural brain abnormalities in frontolimbic areas, comparable to, but less extensive than those reported in established schizophrenia. However, most available data come from ARMS samples from Australia, Europe, and North America while large studies from other populations are missing. We conducted a structural brain magnetic resonance imaging study from a relatively large sample of 69 ARMS individuals and 32 matched healthy controls (HC) recruited from Singapore as part of the Longitudinal Youth At-Risk Study (LYRIKS). We used 2 complementary approaches: a voxel-based morphometry and a surface-based morphometry analysis to extract regional gray and white matter volumes (GMV and WMV) and cortical thickness (CT). At the whole-brain level, we did not find any statistically significant difference between ARMS and HC groups concerning total GMV and WMV or regional GMV, WMV, and CT. The additional comparison of 2 regions of interest, hippocampal, and ventricular volumes, did not return any significant difference either. Several characteristics of the LYRIKS sample like Asian origins or the absence of current illicit drug use could explain, alone or in conjunction, the negative findings and suggest that there may be no dramatic volumetric or CT abnormalities in ARMS. PMID:25745033

  11. Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue.

    PubMed

    Spühler, Isabelle A; Conley, Gaurasundar M; Scheffold, Frank; Sprecher, Simon G

    2016-01-01

    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 labeled 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. PMID:27303270

  12. Simultaneously multiparametric spectroscopic monitoring of tissue viability in the brain and small intestine

    NASA Astrophysics Data System (ADS)

    Tolmasov, Michael; Barbiro-Michaely, Efrat; Mayevsky, Avraham

    2007-02-01

    Under body O II imbalance, the Autonomic Nervous System is responsible for redistribution of blood flow with preference to the most vital organs (brain, heart), while the less vital organs (intestine, GI tract) are hypoperfused. The aim of this study was to develop and use an animal model for real time monitoring of tissue viability in the brain, and the small intestine, under various levels of oxygen and blood supply. Male Wistar rats were anesthetized, the brain cortex and intestinal serosa were exposed and connected by optical fibers to the Multi-Site Multi-Parametric (MSMP) monitoring system. Tissue blood flow (TBF) and mitochondrial NADH redox state were monitored simultaneously in the two organs. The rats were subjected to short anoxia, 20 minutes hypoxia or epinephrine (2& 8μg/kg I.V.). Under oxygen deficiency, cerebral blood flow (CBF) was elevated, whereas intestinal TBF was reduced. Mitochondrial NADH was significantly elevated in both organs. Systemic injection of Adrenaline showed a dose-depended increase in systemic blood pressure and CBF response whereas, intestinal TBF similarly decreased in both doses. In addition, NADH was elevated (reduced form) in the intestine whereas oxidation was observed in the brain. In conclusion, our preliminary results may imply the ability of using of the MSMP for monitoring non-vital organs in order to detect early changes in the balance between oxygen supply and demand in the body.

  13. Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue

    PubMed Central

    Spühler, Isabelle A.; Conley, Gaurasundar M.; Scheffold, Frank; Sprecher, Simon G.

    2016-01-01

    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 labeled 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. PMID:27303270

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

    SciTech Connect

    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.

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

    PubMed Central

    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 < 0.001) to 18 ± 24 mm Hg and increase in CPP after 1 h of gingkolide B infusion from 74 ± 18 to 85 ± 22 mm Hg (P < 0.002). However there was no significant effect on MAP but PbtO2 was maintained in the range of 22-26. The peak lactate/pyruvate ratio was recorded at the time of initiation of osmotherapy (44 ± 20) with an 18% decrease over 2 h following gingkolide B therapy. Also the brain glucose remained unaffected. PMID:26064244

  16. PDT-induced apoptosis in brain tissue in vivo: a retrospective study

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar D.; Portnoy, Michelle; Wilson, Brian C.

    1999-07-01

    The apoptotic response of normal brain and intracranial VX2 tumor following photodynamic therapy mediated by five different photodynamic drugs, Photofrin, ALA, AlClPc, SnET2 and mTHPC, was evaluated in a preliminary retrospective analysis. Rabbit brain, with or without tumor, was treated by PDT with interstitial light delivery. Histological sections at 24 h post PDT were assessed by the TUNEL assay. Confocal fluorescence microscopy was used to determine the total apoptotic cell count and the spatial distribution of apoptotic bodies within the tissue. The data were confirmed qualitatively by light microscopy on adjacent H&E-stained sections. Light-only and drug-only controls produced background levels. The highest apoptotic count was seen with Photofrin. The counts in AlClPc-treated animals were not above the background level, while the other 3 photosensitizers gave intermediate levels. With some, but not all, drugs the spatial distribution of apoptotic bodies correlated well with the light fluence distribution. Apoptosis was seen outside the zone of frank coagulative necrosis. There was not apparent drug-dose dependency at the relatively high doses used here. The retrospective nature of this study did not allow optimization of the treatment parameters. Nevertheless, the findings have potentially significant implications, both for understanding the mechanisms of apoptosis in brain tissue and for improving the clinical use of PDT for treatment of patients with malignant brain tumors.

  17. Optical vortex beam transmission with different OAM in scattering beads and brain tissue media

    NASA Astrophysics Data System (ADS)

    Wang, W. B.; Shi, Lingyan; Lindwasser, Lukas; Marque, Paulo; Lavery, M. P. J.; Alfano, R. R.

    2016-03-01

    Light transmission of Laguerre Gaussian (LG) vortex beams with different orbital angular momentum (OAM) values (L) in scattering beads and mouse brain tissue media were experimentally investigated for the first time in comparison with Gaussian (G) beams. The LG beams with different OAM were generated using a spatial light modulator (SLM) in reflection mode. The scattering beads media consist of various sizes and concentrations of latex beads in water solutions. The transmissions of LG and G beams through scattering beads and brain tissue media were measured with different ratios of sample thicknesses (z) to scattering mean free path (ls) of the turbid media, z/ls. The results indicate that within the ballistic region where z/ls is small, the LG and G beams show no significant difference, while in the diffusive region where z/ls is higher, the vortex beams show higher transmission than G beams. In the diffusive region, the LG beams with higher L values show higher transmission than the beams with lower L values due to the eigen channels in the media. The transition points from the ballistic to diffusive regions for different scattering beads and brain tissue media were studied.

  18. [Characteristics of brain tissue damage in kaolin-induced infantile rat hydrocephalus].

    PubMed

    Okuyama, T; Hashi, K; Okada, T; Sasaki, S

    1986-01-01

    Experimental hydrocephalus was induced by an intracisternal injection of 4% or 40% kaolin suspension in 2 days old Wistar rats. They were examined histologically and microangiographically 2 weeks after the injection of kaolin. Hydrocephalic rats were classified into 2 groups, severe hydrocephalic group A and mild hydrocephalic group B. In group A, a marked enlargement of the entire ventricular system with a thinning of the cerebral mantle was observed. On the other hand, the dilatation of the fourth ventricle was more pronounced compared with the other ventricles in group B. In group A, a spongy appearance of brain tissue was observed in the periventricular white matter accompanied with an intracerebral cavity. In these edematous areas, the lack of carbon black perfusion was apparent indicating an occurrence of microcirculatory disturbances. These microcirculatory disturbances and mechanical compression to the cerebral parenchyma may produce defective brain tissue (intracerebral cavity formation). The ependymal cell walls and subependymal glial cell layers were well preserved in spite of the damaged periventricular white matter. In group A, kaolin was present in the fourth ventricle and Sylvian aqueduct. Subependymal gliosis containing macrophages and newly produced blood vessels were observed in the region between the periventricular brain tissue and kaolin granules. These findings indicate that kaolin may produce changes in the ependymal cell and cerebral parenchyma as well as fibrosis and meningitis in the subarachnoid space. PMID:3964487

  19. Realistic Numerical and Analytical Modeling of Light Scattering in Brain Tissue for Optogenetic Applications123

    PubMed Central

    Meitav, Nizan; Shoham, Shy

    2016-01-01

    Abstract In recent years, optogenetics has become a central tool in neuroscience research. Estimating the transmission of visible light through brain tissue is of crucial importance for controlling the activation levels of neurons in different depths, designing optical systems, and avoiding lesions from excessive power density. The Kubelka–Munk model and Monte Carlo simulations have previously been used to model light propagation through rodents' brain tissue, however, these prior attempts suffer from fundamental shortcomings. Here, we introduce and study two modified approaches for modeling the distributions of light emanating from a multimode fiber and scattering through tissue, using both realistic numerical Monte Carlo simulations and an analytical approach based on the beam-spread function approach. We demonstrate a good agreement of the new methods' predictions both with recently published data, and with new measurements in mouse brain cortical slices, where our results yield a new cortical scattering length estimate of ∼47 µm at λ = 473 nm, significantly shorter than ordinarily assumed in optogenetic applications. PMID:26866055

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

    PubMed

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

    1986-05-01

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

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

    PubMed Central

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

    2016-01-01

    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. PMID:22402104

  2. Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy.

    PubMed

    Yong, William H; Butte, Pramod V; Pikul, Brian K; Jo, Javier A; Fang, Qiyin; Papaioannou, Thanassis; Black, Keith; Marcu, Laura

    2006-01-01

    Neuropathology frozen section diagnoses are difficult in part because of the small tissue samples and the paucity of adjunctive rapid intraoperative stains. This study aims to explore the use of time-resolved laser-induced fluorescence spectroscopy as a rapid adjunctive tool for the diagnosis of glioma specimens and for distinction of glioma from normal tissues intraoperatively. Ten low grade gliomas, 15 high grade gliomas without necrosis, 6 high grade gliomas with necrosis and/or radiation effect, and 14 histologically uninvolved "normal" brain specimens are spectroscopicaly analyzed and contrasted. Tissue autofluorescence was induced with a pulsed Nitrogen laser (337 nm, 1.2 ns) and the transient intensity decay profiles were recorded in the 370-500 nm spectral range with a fast digitized (0.2 ns time resolution). Spectral intensities and time-dependent parameters derived from the time-resolved spectra of each site were used for tissue characterization. A linear discriminant analysis diagnostic algorithm was used for tissue classification. Both low and high grade gliomas can be distinguished from histologically uninvolved cerebral cortex and white matter with high accuracy (above 90%). In addition, the presence or absence of treatment effect and/or necrosis can be identified in high grade gliomas. Taking advantage of tissue autofluorescence, this technique facilitates a direct and rapid investigation of surgically obtained tissue. PMID:16368511

  3. Mathematical model of the effect of ischemia-reperfusion on brain capillary collapse and tissue swelling.

    PubMed

    Mohamed Mokhtarudin, M J; Payne, S J

    2015-05-01

    Restoration of an adequate cerebral blood supply after an ischemic attack is a primary clinical goal. However, the blood-brain barrier may break down after a prolonged ischemia causing the fluid in the blood plasma to filtrate and accumulate into the cerebral tissue interstitial space. Accumulation of this filtration fluid causes the cerebral tissue to swell, a condition known as vasogenic oedema. Tissue swelling causes the cerebral microvessels to be compressed, which may further obstruct the blood flow into the tissue, thus leading to the no-reflow phenomenon or a secondary ischemic stroke. The actual mechanism of this however is still not fully understood. A new model is developed here to study the effect of reperfusion on the formation of vasogenic oedema and cerebral microvessel collapse. The formation of vasogenic oedema is modelled using the capillary filtration equation while vessel collapse is modelled using the tube law of microvessel. Tissue swelling is quantified in terms of displacement, which is modelled using poroelastic theory. The results show that there is an increase in tissue displacement and interstitial pressure after reperfusion. In addition, the results also show that vessel collapse can occur at high value of reperfusion pressure, low blood osmotic pressure, high cerebral capillary permeability and low cerebral capillary stiffness. This model provides insight on the formation of ischemia-reperfusion injury by tissue swelling and vessel collapse. PMID:25749185

  4. Influence of brain tumors on the MR spectra of healthy brain tissue.

    PubMed

    Busch, M; Liebenrodt, K; Gottfried, S; Weiland, E; Vollmann, W; Mateiescu, S; Winter, S; Lange, S; Sahinbas, H; Baier, J; van Leeuwen, P; Grönemeyer, D

    2011-01-01

    The neurochemical environment of nontumorous white matter tissue was investigated in 135 single voxel spectra of "healthy" white matter regions of 43 tumor patients and 129 spectra of 52 healthy subjects. Spectra were acquired with short TE and TR values. With the data of tumor patients, it was examined whether differences were caused by the tumor itself or aggressive tumor therapies as confounding factors. Comparing the spectra of both classes, an excellent differentiation was possible based on the metabolite peak of N-acetylaspartate (P ≈ 0) and myoinositol (P < 0.03). The area under curve of the receiver operating characteristic was calculated as 0.86 and 0.62, respectively. With linear discriminant analysis using combinations of integrals, a prediction was possible, whether a spectrum belonged to the patient or the healthy subject class with an overall accuracy above 80%. The confounding factors could be ruled out as source of the differences. The results show strong evidence for an influence of malignant growth on the biochemical environment of nontumorous white matter tissue. Because of the T(1) weighting, the measured differences between both classes were most likely concentration changes interfered by T(1) effects. The underlying processes will be subject of future studies. PMID:20859993

  5. Identification of some volatile endogenous constituents in rat brain tissue and the effects of lithium carbonate and chloral hydrate.

    PubMed

    Politzer, I R; McDonald, L K; Laseter, J L

    1976-11-01

    Nine endogenous volatile compounds were found in rat brain tissue, and were identified by mass spectrometry as chloroform, a 5-C-aldehyde, dimethyl disulphide, 2,5-dimethyl tetrahydrofuran, a 8-C-alkane, xylene, 2-heptanone, heptaldehyde and 2-n-pentylfuran. Using gas chromatographic and gas chromatographic mass spectrometric techniques, it was established that lithium carbonate did not induce the production of detectable amounts of any new volatile compounds in brain tissue. However, after administration of chloral hydrate, trichloroethanol, a compound not normally present in rat brain tissue, was found to be present. PMID:996360

  6. Reversal of brain metabolic abnormalities following treatment of AIDS dementia complex with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine): a PET-FDG study

    SciTech Connect

    Brunetti, A.; Berg, G.; Di Chiro, G.; Cohen, R.M.; Yarchoan, R.; Pizzo, P.A.; Broder, S.; Eddy, J.; Fulham, M.J.; Finn, R.D.

    1989-05-01

    Brain glucose metabolism was evaluated in four patients with acquired immunodeficiency syndrome (AIDS) dementia complex using (/sup 18/F)fluorodeoxyglucose (FDG) and positron emission tomography (PET) scans at the beginning of therapy with 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine), and later in the course of therapy. In two patients, baseline, large focal cortical abnormalities of glucose utilization were reversed during the course of therapy. In the other two patients, the initial PET study did not reveal pronounced focal alterations, while the post-treatment scans showed markedly increased cortical glucose metabolism. The improved cortical glucose utilization was accompanied in all patients by immunologic and neurologic improvement. PET-FDG studies can detect cortical metabolic abnormalities associated with AIDS dementia complex, and may be used to monitor the metabolic improvement in response to AZT treatment.

  7. New tissue priors for improved automated classification of subcortical brain structures on MRI.

    PubMed

    Lorio, S; Fresard, S; Adaszewski, S; Kherif, F; Chowdhury, R; Frackowiak, R S; Ashburner, J; Helms, G; Weiskopf, N; Lutti, A; Draganski, B

    2016-04-15

    Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age-related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel-based morphometry in both healthy and diseased brains. PMID:26854557

  8. New tissue priors for improved automated classification of subcortical brain structures on MRI☆

    PubMed Central

    Lorio, S.; Fresard, S.; Adaszewski, S.; Kherif, F.; Chowdhury, R.; Frackowiak, R.S.; Ashburner, J.; Helms, G.; Weiskopf, N.; Lutti, A.; Draganski, B.

    2016-01-01

    Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age-related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel-based morphometry in both healthy and diseased brains. PMID:26854557

  9. Brain MRI abnormalities and spectrum of neurological and clinical findings in three patients with proximal 16p11.2 microduplication.

    PubMed

    Filges, Isabel; Sparagana, Steven; Sargent, Michael; Selby, Kathryn; Schlade-Bartusiak, Kamilla; Lueder, Gregg T; Robichaux-Viehoever, Amy; Schlaggar, Bradley L; Shimony, Joshua S; Shinawi, Marwan

    2014-08-01

    The phenotype of recurrent ∼600 kb microdeletion and microduplication on proximal 16p11.2 is characterized by a spectrum of neurodevelopmental impairments including developmental delay and intellectual disability, epilepsy, autism and psychiatric disorders which are all subject to incomplete penetrance and variable expressivity. A variety of brain MRI abnormalities were reported in patients with 16p11.2 rearrangements, but no systematic correlation has been studied among patients with similar brain anomalies, their neurodevelopmental and clinical phenotypes. We present three patients with the proximal 16p11.2 microduplication exhibiting significant developmental delay, anxiety disorder and other variable clinical features. Our patients have abnormal brain MRI findings of cerebral T2 hyperintense foci (3/3) and ventriculomegaly (2/3). The neuroradiological or neurological findings in two cases prompted an extensive diagnostic work-up. One patient has exhibited neurological regression and progressive vision impairment and was diagnosed with juvenile neuronal ceroid-lipofuscinosis. We compare the clinical course and phenotype of these patients in regard to the clinical significance of the cerebral lesions and the need for MRI surveillance. We conclude that in all three patients the lesions were not progressive, did not show any sign of malignant transformation and could not be correlated to specific clinical features. We discuss potential etiologic mechanisms that may include overexpression of genes within the duplicated region involved in control of cell proliferation and complex molecular mechanisms such as the MAPK/ERK pathway. Systematic studies in larger cohorts are needed to confirm our observation and to establish the prevalence and clinical significance of these neuroanatomical abnormalities in patients with 16p11.2 duplications. PMID:24891046

  10. International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods.

    PubMed

    Blümcke, Ingmar; Aronica, Eleonora; Miyata, Hajime; Sarnat, Harvey B; Thom, Maria; Roessler, Karl; Rydenhag, Bertil; Jehi, Lara; Krsek, Pavel; Wiebe, Samuel; Spreafico, Roberto

    2016-03-01

    Epilepsy surgery is an effective treatment in many patients with drug-resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging (MRI)-visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic diagnosis and classification of epileptogenic brain lesions are helpful for clinical correlation, outcome stratification, and patient management. However, application of international consensus classification systems to common epileptic pathologies (e.g., focal cortical dysplasia [FCD] and hippocampal sclerosis [HS]) necessitates standardized protocols for neuropathologic workup of epilepsy surgery specimens. To this end, the Task Force of Neuropathology from the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods developed a consensus standard operational procedure for tissue inspection, distribution, and processing. The aims are to provide a systematic framework for histopathologic workup, meeting minimal standards and maximizing current and future opportunities for morphofunctional correlations and molecular studies for both clinical care and research. Whenever feasible, anatomically intact surgical specimens are desirable to enable systematic analysis in selective hippocampectomies, temporal lobe resections, and lesional or nonlesional neocortical samples. Correct orientation of sample and the sample's relation to neurophysiologically aberrant sites requires good communication between pathology and neurosurgical teams. Systematic tissue sampling of 5-mm slabs along a defined anatomic axis and application of a limited immunohistochemical panel will ensure a reliable differential diagnosis of main pathologies encountered in epilepsy surgery. PMID:26839983

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

    SciTech Connect

    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.

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

    NASA Astrophysics Data System (ADS)

    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

  13. Analysis of the influence of handset phone position on RF exposure of brain tissue.

    PubMed

    Ghanmi, Amal; Varsier, Nadège; Hadjem, Abdelhamid; Conil, Emmanuelle; Picon, Odile; Wiart, Joe

    2014-12-01

    Exposure to mobile phone radio frequency (RF) electromagnetic fields depends on many different parameters. For epidemiological studies investigating the risk of brain cancer linked to RF exposure from mobile phones, it is of great interest to characterize brain tissue exposure and to know which parameters this exposure is sensitive to. One such parameter is the position of the phone during communication. In this article, we analyze the influence of the phone position on the brain exposure by comparing the specific absorption rate (SAR) induced in the head by two different mobile phone models operating in Global System for Mobile Communications (GSM) frequency bands. To achieve this objective, 80 different phone positions were chosen using an experiment based on the Latin hypercube sampling (LHS) to select a representative set of positions. The averaged SAR over 10 g (SAR10 g) in the head, the averaged SAR over 1 g (SAR1 g ) in the brain, and the averaged SAR in different anatomical brain structures were estimated at 900 and 1800 MHz for the 80 positions. The results illustrate that SAR distributions inside the brain area are sensitive to the position of the mobile phone relative to the head. The results also show that for 5-10% of the studied positions the SAR10 g in the head and the SAR1 g in the brain can be 20% higher than the SAR estimated for the standard cheek position and that the Specific Anthropomorphic Mannequin (SAM) model is conservative for 95% of all the studied positions. PMID:25263784

  14. Clinical feasibility of using mean apparent propagator (MAP) MRI to characterize brain tissue microstructure.

    PubMed

    Avram, Alexandru V; Sarlls, Joelle E; Barnett, Alan S; Özarslan, Evren; Thomas, Cibu; Irfanoglu, M Okan; Hutchinson, Elizabeth; Pierpaoli, Carlo; Basser, Peter J

    2016-02-15

    Diffusion tensor imaging (DTI) is the most widely used method for characterizing noninvasively structural and architectural features of brain tissues. However, the assumption of a Gaussian spin displacement distribution intrinsic to DTI weakens its ability to describe intricate tissue microanatomy. Consequently, the biological interpretation of microstructural parameters, such as fractional anisotropy or mean diffusivity, is often equivocal. We evaluate the clinical feasibility of assessing brain tissue microstructure with mean apparent propagator (MAP) MRI, a powerful analytical framework that efficiently measures the probability density function (PDF) of spin displacements and quantifies useful metrics of this PDF indicative of diffusion in complex microstructure (e.g., restrictions, multiple compartments). Rotation invariant and scalar parameters computed from the MAP show consistent variation across neuroanatomical brain regions and increased ability to differentiate tissues with distinct structural and architectural features compared with DTI-derived parameters. The return-to-origin probability (RTOP) appears to reflect cellularity and restrictions better than MD, while the non-Gaussianity (NG) measures diffusion heterogeneity by comprehensively quantifying the deviation between the spin displacement PDF and its Gaussian approximation. Both RTOP and NG can be decomposed in the local anatomical frame for reference determined by the orientation of the diffusion tensor and reveal additional information complementary to DTI. The propagator anisotropy (PA) shows high tissue contrast even in deep brain nuclei and cortical gray matter and is more uniform in white matter than the FA, which drops significantly in regions containing crossing fibers. Orientational profiles of the propagator computed analytically from the MAP MRI series coefficients allow separation of different fiber populations in regions of crossing white matter pathways, which in turn improves our

  15. A comparison of hyperelastic constitutive models applicable to brain and fat tissues

    PubMed Central

    Mihai, L. Angela; Chin, LiKang; Janmey, Paul A.; Goriely, Alain

    2015-01-01

    In some soft biological structures such as brain and fat tissues, strong experimental evidence suggests that the shear modulus increases significantly under increasing compressive strain, but not under tensile strain, whereas the apparent Young's elastic modulus increases or remains almost constant when compressive strain increases. These tissues also exhibit a predominantly isotropic, incompressible behaviour. Our aim is to capture these seemingly contradictory mechanical behaviours, both qualitatively and quantitatively, within the framework of finite elasticity, by modelling a soft tissue as a homogeneous, isotropic, incompressible, hyperelastic material and comparing our results with available experimental data. Our analysis reveals that the Fung and Gent models, which are typically used to model soft tissues, are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney–Rivlin models used for elastomers. However, a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments. Our findings provide explicit models suitable for integration in large-scale finite-element computations. PMID:26354826

  16. A comparison of hyperelastic constitutive models applicable to brain and fat tissues.

    PubMed

    Mihai, L Angela; Chin, LiKang; Janmey, Paul A; Goriely, Alain

    2015-09-01

    In some soft biological structures such as brain and fat tissues, strong experimental evidence suggests that the shear modulus increases significantly under increasing compressive strain, but not under tensile strain, whereas the apparent Young's elastic modulus increases or remains almost constant when compressive strain increases. These tissues also exhibit a predominantly isotropic, incompressible behaviour. Our aim is to capture these seemingly contradictory mechanical behaviours, both qualitatively and quantitatively, within the framework of finite elasticity, by modelling a soft tissue as a homogeneous, isotropic, incompressible, hyperelastic material and comparing our results with available experimental data. Our analysis reveals that the Fung and Gent models, which are typically used to model soft tissues, are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney-Rivlin models used for elastomers. However, a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments. Our findings provide explicit models suitable for integration in large-scale finite-element computations. PMID:26354826

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

    PubMed Central

    Landahl, Eric C.; Antipova, Olga; Bongaarts, Angela; Barrea, Raul; Berry, Robert; Binder, Lester I.; Irving, Thomas; Orgel, Joseph; Vana, Laurel

    2011-01-01

    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 labs have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in x-ray diffraction that is not observed in healthy tissue. One observed periodicity (4.2 Å) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein. PMID:21876609

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

    PubMed

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

    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 labs have done previously. We demonstrate that thiazine red-enhanced regions within the tissue show periodic structure in x-ray diffraction that is not observed in healthy tissue. One observed periodicity (4.2 Å) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein. PMID:21876609

  19. Quantifying the local tissue volume and composition in individual brains with MRI

    PubMed Central

    Mezer, Aviv; Yeatman, Jason D.; Stikov, Nikola; Kay, Kendrick N.; Cho, Nam–Joon; Dougherty, Robert F.; Perry, Michael L.; Parvizi, Josef; Hua, Le H.; Butts-Pauly, Kim; Wandell, Brian

    2013-01-01

    We describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent, quantitative estimate of macromolecular volume can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition. PMID:24185694

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

    NASA Astrophysics Data System (ADS)

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

    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 Å) is characteristic of cross-beta sheet structure, consistent with previous results from powder diffraction studies performed on purified, dried tau protein.

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

    SciTech Connect

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

    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.

  2. Dual-porosity poroviscoelasticity and quantitative hydromechanical characterization of the brain tissue with experimental hydrocephalus data.

    PubMed

    Mehrabian, Amin; Abousleiman, Younane N; Mapstone, Timothy B; El-Amm, Christian A

    2015-11-01

    Hydromechanical brain models often involve constitutive relations which must account for soft tissue deformation and creep, together with the interstitial fluid movement and exchange through capillaries. The interaction of rather unknown mechanisms which produce, absorb, and circulate the cerebrospinal fluid within the central nervous system can further add to their complexity. Once proper models for these phenomena or processes are selected, estimation of the associated parameters could be even more challenging. This paper presents the results of a consistent, coupled poroviscoelastic modeling and characterization of the brain tissue as a dual-porosity system. The model draws from Biot's theory of poroviscoelasticity, and adopts the generalized Kelvin's rheological description of the viscoelastic tissue behavior. While the interstitial space serves as the primary porosity through which the bulk flow of the interstitial fluid occurs, a secondary porosity network comprising the capillaries and venous system allows for its partial absorption into the blood. The correspondence principle is used in deriving a time-dependent analytical solution to the proposed model. It allows for identical poroelastic formulation of the original poroviscoelastic problem in the Laplace transform space. Hydrocephalus generally refers to a class of medical conditions which share the ventricles enlargement as a common feature. A set of published data from induced hydrocephalus and follow-up perfusion of cats' brains is used for quantitative characterization of the proposed model. A selected portion of these data including the ventricular volume and rate of fluid absorption from the perfused brain, together with the forward model solution, is utilized via an inverse problem technique to find proper estimations of the model parameters. Results show significant improvement in model predictions of the experimental data. The convoluted and coupled solution results are presented through the time

  3. A fully automatic unsupervised segmentation framework for the brain tissues in MR images

    NASA Astrophysics Data System (ADS)

    Mahmood, Qaiser; Chodorowski, Artur; Ehteshami Bejnordi, Babak; Persson, Mikael

    2014-03-01

    This paper presents a novel fully automatic unsupervised framework for the segmentation of brain tissues in magnetic resonance (MR) images. The framework is a combination of our proposed Bayesian-based adaptive mean shift (BAMS), a priori spatial tissue probability maps and fuzzy c-means. BAMS is applied to cluster the tissues in the joint spatialintensity feature space and then a fuzzy c-means algorithm is employed with initialization by a priori spatial tissue probability maps to assign the clusters into three tissue types; white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). The proposed framework is validated on multimodal synthetic as well as on real T1-weighted MR data with varying noise characteristics and spatial intensity inhomogeneity. The performance of the proposed framework is evaluated relative to our previous method BAMS and other existing adaptive mean shift framework. Both of these are based on the mode pruning and voxel weighted k-means algorithm for classifying the clusters into WM, GM and CSF tissue. The experimental results demonstrate the robustness of the proposed framework to noise and spatial intensity inhomogeneity, and that it exhibits a higher degree of segmentation accuracy in segmenting both synthetic and real MR data compared to competing methods.

  4. Effects of compression injury on brain mitochondrial and tissue viability evaluated by a multiparametric monitoring system

    NASA Astrophysics Data System (ADS)

    Barbiro-Michaely, Efrat; Bachbut, Galit; Mayevsky, Avraham

    2008-02-01

    Neurosurgical procedures involve brain compression created by retractors. Although it is clear that retractors are causing damage to the brain tissue, the pathophysiology of the retraction was not investigated in details. In the present study we used the multiparametric monitoring approach for real time evaluation of mitochondrial function, hemodynamic, ionic and electrical activities monitored contralaterally to the retractor placement on the brain. The aims of the study were to test the effects of retractor size and severity of the compression on the degree of damage to the cerebral tissue. A special probe was lowered towards the cerebral cortex, (2mm and 4mm in depth) using a micromanipulator. Compression lasted for 30 minutes, than the retractor was elevated back to its initial position and monitoring continued for two hours. Additionally, two sizes of retractors were used 6mm and 3mm in diameter, the 3mm retractor included an intracranial pressure (ICP) probe. The results show that the combination of a large retractor with the depth of 4mm yielded high mortality rate (62%) of the rats while the use of a smaller retractor decreased significantly the percentage of mortality. Also, compression to the depth of 4mm increased tissue injury as compared to 2mm depth. In conclusion, the present study raises the importance and significance of multiparametric monitoring, and not only ICP and cerebral blood flow of the areas nearby the retractor position and not only the retraction site, as well as the effect of the retractor size on the damage induced to the cerebral tissue.

  5. Ex vivo viscoelastic characterization of head and neck tissue abnormalities using ultrasound-stimulated vibro-acoustography (USVA)

    NASA Astrophysics Data System (ADS)

    Maccabi, Ashkan; Garritano, James; Arshi, Armin; Saddik, George; Tajudeen, Bobby A.; St. John, Maie; Grundfest, Warren S.; Taylor, Zachary D.

    2014-03-01

    In the absence of an imaging technique that offers a highly dynamic range detection of malignant tissue intra-operatively, surgeons are often forced to excise excess healthy tissue to ensure clear margins of resection. Techniques that are currently used in the detection of tumor regions include palpation, optical coherence tomography (OCT) elastography, dye injections, and conventional ultrasound to pinpoint the affected area. However, these methods suffer from limitations such as minimal specificity, low contrast, and limited depth of penetration. Lack of specificity and low contrast result in the production of vague disease margins and fail to provide a reliable guidance tool for surgeons. The proposed work presents an alternative diagnostic technique, ultrasound-stimulated vibro-acoustography (USVA), which may potentially provide surgeons with detailed intra-operative imagery characterized by enhanced structural boundaries and well-defined borders based on the viscoelastic properties of tissues. We demonstrate selective imaging using ex vivo tissue samples of head and neck squamous cell carcinoma (HNSCC) with the presence of both malignant and normal areas. Spatially resolved maps of varying acoustic properties were generated and show good contrast between the areas of interest. While the results are promising, determining the precision and sensitivity of the USVA imaging system in identifying boundary regions as well as intensities of ex vivo tissue targets may provide additional information to non-invasively assess confined regions of diseased tissues from healthy areas.

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

    PubMed Central

    Sun, Hongtao; Zheng, Maohua; Wang, Yanmin; Diao, Yunfeng; Zhao, Wanyong; Wei, Zhengjun

    2016-01-01

    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. PMID:27601907

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

    PubMed Central

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

    2015-01-01

    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. PMID:26108566

  8. Autophagy is upregulated in brain tissues of pigeons exposed to avermectin.

    PubMed

    Qu, Jianping; Li, Ming; Zhao, Fuqing; Liu, Ci; Zhang, Ziwei; Xu, Shiwen; Li, Shu

    2015-03-01

    Avermectin (AVM) is used in agriculture and veterinary medicine for the prevention of parasitic diseases; AVM is the active component of some insecticidal and nematicidal products. Residues of AVM drugs or their metabolites in livestock feces have toxic effects on non-target aquatic and terrestrial organisms. In this study, changes in the levels of autophagy related genes and ultrastructure in pigeon brain tissues after subchronic exposure to AVM for 30, 60 and 90 d were investigated. The decrease in the mRNA levels of TORC1 and TORC2 and increase in the mRNA levels of LC3, Beclin 1, Dynein, ATG5 and ATG4B and the increase in the protein levels of LC3, Beclin 1 and Dynein in a dose- and time-dependent manner in the pigeon brain were observed. The number of autophagic vacuoles in the cerebrum, cerebellum and optic lobe increased significantly with the concentration of AVM and the exposure time. We found that the changes in the levels of autophagy related genes and the ultrastructure in the cerebrum were more obvious than in the cerebellum and the optic lobe. The results suggest that AVM could induce autophagy in pigeon brain tissues. The information presented in this study is helpful for understanding the mechanism of AVM-induced autophagy in birds. PMID:25497772

  9. Micromotion-induced dynamic effects from a neural probe and brain tissue interface

    NASA Astrophysics Data System (ADS)

    Polanco, Michael; Yoon, Hargsoon; Bawab, Sebastian

    2014-04-01

    Neural probes contain the potential to cause injury to surrounding neural cells due to a discrepancy in stiffness values between them and the surrounding brain tissue when subjected to mechanical micromotion of the brain. To evaluate the effects of the mechanical mismatch, a series of dynamic simulations are conducted to better understand the design enhancements required to improve the feasibility of the neuron probe. The simulations use a nonlinear transient explicit finite element code, LS-DYNA. A three-dimensional quarter-symmetry finite element model is utilized for the transient analysis to capture the time-dependent dynamic deformations on the brain tissue from the implant as a function of different frequency shapes and stiffness values. When micromotion-induced pulses are applied, reducing the neuron probe stiffness by three orders of magnitude leads up to a 41.6% reduction in stress and 39.1% reduction in strain. The simulation conditions assume a case where sheath bonding has begun to take place around the probe implantation site, but no full bond to the probe has occurred. The analyses can provide guidance on the materials necessary to design a probe for injury reduction.

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

    PubMed

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

    2015-01-01

    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. PMID:26108566

  11. Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue

    PubMed Central

    Lilge, L; Portnoy, M; Wilson, B C

    2000-01-01

    The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET 2), and meta-tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. © 2000 Cancer Research Campaign PMID:10993661

  12. Apoptosis induced in vivo by photodynamic therapy in normal brain and intracranial tumour tissue.

    PubMed

    Lilge, L; Portnoy, M; Wilson, B C

    2000-10-01

    The apoptotic response of normal brain and intracranial VX2 tumour following photodynamic therapy (PDT) mediated by 5 different photosensitizers (Photofrin, 5-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX), chloroaluminium phthalocyanine (AlCIPc), Tin Ethyl Etiopurpurin (SnET(2)), and meta -tetra(hydroxyphenyl)chlorin (m THPC)) was evaluated following a previous analysis which investigated the necrotic tissue response to PDT at 24 h post treatment. Free DNA ends, produced by internucleosomal DNA cleavage in apoptotic cells, were stained using a TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling) assay. Confocal laser scanning microscopy (CLSM) was used to quantify the local incidence of apoptosis and determine its spatial distribution throughout the brain. The incidence of apoptosis was confirmed by histopathology, which demonstrated cell shrinkage, pyknosis and karyorrhexis. At 24 h post PDT, AlClPc did not cause any detectable apoptosis, while the other photosensitizers produced varying numbers of apoptotic cells near the region of coagulative necrosis. The apoptotic response did not appear to be related to photosensitizer dose. These results suggest that at this time point, a minimal and fairly localized apoptotic effect is produced in brain tissues, the extent of which depends largely on the particular photosensitizer. PMID:10993661

  13. Epileptic seizures induce structural and functional alterations on brain tissue membranes.

    PubMed

    Turker, Sevgi; Severcan, Mete; Ilbay, Gul; Severcan, Feride

    2014-12-01

    Epilepsy is characterized by disruption of balance between cerebral excitation and inhibition, leading to recurrent and unprovoked convulsions. Studies are still underway to understand mechanisms lying epileptic seizures with the aim of improving treatment strategies. In this context, the research on brain tissue membranes gains importance for generation of epileptic activities. In order to provide additional information for this field, we have investigated the effects of pentylenetetrazol-induced and audiogenetically susceptible epileptic seizures on structure, content and function of rat brain membrane components using Fourier transform infrared (FT-IR) spectroscopy. The findings have shown that both two types of epileptic seizures stimulate the variations in the molecular organization of membrane lipids, which have potential to influence the structures in connection with functions of membrane proteins. Moreover, less fluid lipid structure and a decline in content of lipids obtained from the ratio of CH3 asym/lipid, CH2 asym/lipid, CO/lipid, and olefinicCH/lipid and the areas of the PO2 symmetric and asymmetric modes were observed. Moreover, based on IR data the changes in the conformation of proteins were predicted by neural network (NN) analysis, and displayed as an increase in random coil despite a decrease in beta sheet. Depending on spectral parameters, we have successfully differentiated treated samples from the control by principal component analysis (PCA) and cluster analysis. In summary, FT-IR spectroscopy may offer promising attempt to identify compositional, structural and functional alterations in brain tissue membranes resulting from epileptic activities. PMID:25194682

  14. Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

    PubMed Central

    Shweikeh, Faris; Bukavina, Laura; Saeed, Kashif; Sarkis, Reem; Suneja, Aarushi; Sweiss, Fadi; Drazin, Doniel

    2014-01-01

    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. PMID:24757391

  15. The natural xanthone alpha-mangostin reduces oxidative damage in rat brain tissue.

    PubMed

    Márquez-Valadez, Berenice; Lugo-Huitrón, Rafael; Valdivia-Cerda, Verónica; Miranda-Ramírez, Luis Rubén; Pérez-De La Cruz, Verónica; González-Cuahutencos, Octavio; Rivero-Cruz, Isabel; Mata, Rachel; Santamaría, Abel; Pedraza-Chaverrí, José

    2009-02-01

    The antiperoxidative properties of alpha-mangostin, a xanthone isolated from mangosteen fruit, were tested for the first time in nerve tissue exposed to different toxic insults. Two reliable biological preparations (rat brain homogenates and synaptosomal P2 fractions) were exposed to the toxic actions of a free radical generator (ferrous sulfate), an excitotoxic agent (quinolinate), and a mitochondrial toxin (3-nitropropionate). alpha-Mangostin decreased the lipoperoxidativ