Voxelwise evaluation of white matter volumes in first-episode psychosis

The occurrence of white matter (WM) abnormalities in psychotic disorders has been suggested by several studies investigating brain pathology and diffusion tensor measures, but evidence assessing regional WM morphometry is still scarce and conflicting. In the present study, 122 individuals with first-episode psychosis (FEP) (62 fulfilling criteria for schizophrenia/schizophreniform disorder, 26 psychotic bipolar I disorder, and 20 psychotic major depressive disorder) underwent magnetic resonance imaging, as well as 94 epidemiologically recruited controls. Images were processed with the Statistical Parametric Mapping (SPM2) package, and voxel-based morphometry was used to compare groups (t-test) and subgroups (ANOVA). Initially, no regional WM abnormalities were observed when both groups (overall FEP group versus controls) and subgroups (i.e., schizophrenia/schizophreniform, psychotic bipolar I disorder, psychotic depression, and controls) were compared. However, when the voxelwise analyses were repeated excluding subjects with comorbid substance abuse or dependence, the resulting statistical maps revealed a focal volumetric reduction in right frontal WM, corresponding to the right middle frontal gyral WM/third subcomponent of the superior longitudinal fasciculus, in subjects with schizophrenia/schizophreniform disorder (n = 40) relative to controls (n = 89). Our results suggest that schizophrenia/schizophreniform disorder is associated with right frontal WM volume decrease at an early course of the illness. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology

Background: schizophrenia's endophenotipic profile is not only generally complex, but often varies from case to case. The perspective of trying to define specific anatomic correlates of the syndrome has led to disappointing results. In that context, neurophysiologic hypotheses (e. g. glutamatergic hypothesis) and connectivity hypotheses became prominent. Nevertheless, despite their commitment to the principle of denying 'localist' views and approaching the syndrome's endophenotype from a whole brain perspective, efforts to integrate both have not flourished at this moment in time. Objectives: This paper aims to introduce a new etiological model that integrates the glutamatergic and the WM (WM) hypotheses of schizophrenia's etiology. This model proposes to serve as a framework in order to relate to patterns of brain abnormalities from the onset of the syndrome to stages of advanced chronification. Highlights: Neurotransmitter abnormalities forego noticeable WM abnormalities. The former, chiefly represented by NMDAR hypo-function and associated molecular cascades, is related to the first signs of cell loss. This process is both directly and indirectly integrated to the underpinning of WM structural abnormalities; not only is the excess of glutamate toxic to the WM, but its disruption is associated to the expression of known genetic risk factors (e. g., NRG-1). A second level of the model develops the idea that abnormal neurotransmission within specific neural populations ('motifs') impair particular cognitive abilities, while subsequent WM structural abnormalities impair the integration of brain functions and multimodality. As a result of this two-stage dynamic, the affected individual progresses from experiencing specific cognitive and psychological deficits, to a condition of cognitive and existential fragmentation, linked to hardly reversible decreases in psychosocial functioning.

Cerebral White Matter Oxidation and Nitrosylation in Young Rodents With Kaolin-Induced Hydrocephalus

Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities of the antioxidant enzymes catalase and glutathione peroxidase were not increased, and altered hypoxia-inducible factor 1 alpha was not detected by quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined by quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.

Impaired blood-brain/spinal cord barrier in ALS patients

Vascular pathology, including blood-brain/spinal cord barrier (BBB/BSCB) alterations, has recently been recognized as a key factor possibly aggravating motor neuron damage, identifying a neurovascular disease signature for ALS. However, BBB/BSCB competence in sporadic ALS (SALS) is still undetermined. In this study, BBB/BSCB integrity in postmortem gray and white matter of medulla and spinal cord tissue from SALS patients and controls was investigated. Major findings include (1) endothelial cell damage and pericyte degeneration, (2) severe intra- and extracellular edema, (3) reduced CD31 and CD105 expressions in endothelium, (4) significant accumulation of perivascular collagen IV, and fibrin deposits (5) significantly increased microvascular density in lumbar spinal cord, (6) IgG microvascular leakage, (7) reduced tight junction and adhesion protein expressions. Microvascular barrier abnormalities determined in gray and white matter of the medulla, cervical, and lumbar spinal cord of SALS patients are novel findings. Pervasive barrier damage discovered in ALS may have implications for disease pathogenesis and progression, as well as for uncovering novel therapeutic targets. (C) 2012 Elsevier B.V. All rights reserved.

DTI voxelwise analysis did not differentiate older depressed patients from older subjects without depression

Introduction: Neuroimaging has been widely used in studies to investigate depression in the elderly because it is a noninvasive technique, and it allows the detection of structural and functional brain alterations. Fractional anisotropy (FA) and mean diffusivity (MD) are neuroimaging indexes of the microstructural integrity of white matter, which are measured using diffusion tensor imaging (DTI). The aim of this study was to investigate differences in FA or MD in the entire brain without a previously determined region of interest (ROI) between depressed and non-depressed elderly patients. Method: Brain magnetic resonance imaging scans were obtained from 47 depressed elderly patients, diagnosed according to DSM-IV criteria, and 36 healthy elderly patients as controls. Voxelwise statistical analysis of FA data was performed using tract-based spatial statistics (TBSS). Results: After controlling for age, no significant differences among FA and MD parameters were observed in the depressed elderly patients. No significant correlations were found between cognitive performance and FA or MD parameters. Conclusion: There were no significant differences among FA or MD values between mildly or moderately depressed and non-depressed elderly patients when the brain was analyzed without a previously determined ROI. (C) 2012 Elsevier Ltd. All rights reserved.

0.1T magnetic resonance image in the study of experimental hydrocephalus in rats. Accuracy of the method in the measurements of the ventricular size

PURPOSE: To investigate the accuracy of 1.0T Magnetic Resonance Imaging (MRI) to measure the ventricular size in experimental hydrocephalus in pup rats. METHODS: Wistar rats were subjected to hydrocephalus by intracisternal injection of 20% kaolin (n=13). Ten rats remained uninjected to be used as controls. At the endpoint of experiment animals were submitted to MRI of brain and killed. The ventricular size was assessed using three measures: ventricular ratio (VR), the cortical thickness (Cx) and the ventricles area (VA), performed on photographs of anatomical sections and MRI. RESULTS: The images obtained through MR present enough quality to show the lateral ventricular cavities but not to demonstrate the difference between the cortex and the white matter, as well as the details of the deep structures of the brain. There were no statistically differences between the measures on anatomical sections and MRI of VR and Cx (p=0.9946 and p=0.5992, respectively). There was difference between VA measured on anatomical sections and MRI (p<0.0001). CONCLUSION: The parameters obtained through 1.0T MRI were sufficient in quality to individualize the ventricular cavities and the cerebral cortex, and to calculate the ventricular ratio in hydrocephalus rats when compared to their respective anatomic slice.

Vascular dementia: Different forms of vessel disorders contribute to the development of dementia in the elderly brain

The diagnosis of vascular dementia (VaD) describes a group of various vessel disorders with different types of vascular lesions that finally contribute to the development of dementia. Most common forms of VaD in the elderly brain are subcortical vascular encephalopathy, strategic infarct dementia, and the multi infarct encephalopathy. Hereditary forms of VaD are rare. Most common is the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Sporadic forms of VaD are caused by degenerative vessel disorders such as atherosclerosis, small vessel disease (SVD) including small vessel arteriosclerosis, arteriolosclerosis, and lipohyalinosis, and cerebral amyloid angiopathy (CAA). Less frequently inflammatory vessel disorders and tumor-associated vessel lesions (e. g. angiocentric T-cell or angiotropic large cell lymphoma) can cause symptoms of dementia. Here, we review and discuss the impact of vessel disorders to distinct vascular brain tissue lesions and to the development of dementia in elderly individuals. The impact of coexisting neurodegenerative pathology in the elderly brain to VaD as well as the correlation between SVD and CAA expansion in the brain parenchyma with that of Alzheimer's disease (AD)-related pathology is highlighted. We conclude that "pure" VaD is rare and most frequently caused by infarctions. However, there is a significant contribution of vascular lesions and vessel pathology to the development of dementia that may go beyond tissue damage due to vascular lesions. Insufficient blood blow and alterations of the perivascular drainage mechanisms of the brain may also lead to a reduced protein clearance from extracellular space and subsequent increase of proteins in the brain parenchyma, such as the amyloid beta-protein, and foster, thereby, the development of AD-related neurodegeneration. As such, it seems to be important for clinical practice to consider treatment of potentially coexisting AD pathology in cognitively impaired patients with vascular lesions. (C) 2012 Elsevier Inc. All rights reserved.

Decreased Reelin Expression in the Left Prefrontal Cortex (BA9) in Chronic Schizophrenia Patients

Background: Reelin is under epigenetic control and has been reported to be decreased in cortical regions in schizophrenia. Methods: To establish if expression of reelin is altered in specific cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of reelin in a postmortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral postmortem samples (dorsolateral prefrontal cortex BA9 and BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1-3, hippocampus, CA4, mediodorsal nucleus of the thalamus) from 12 schizophrenia patients with 13 normal subjects investigating gene expression of reelin in the gray and white matter of both hemispheres by in situ-hybridization. Results: The left prefrontal area (BA9) of schizophrenia patients revealed a decreased expression of reelin-mRNA of 29.1% in the white (p = 0.022) and 13.6% in the gray matter (p = 0.007) compared to the control group. None of the other regions examined showed any statistically significant differences. Conclusion: Since reelin is responsible for migration and synapse formation, the decreased gene expression of reelin in the left prefrontal area of schizophrenia patients points to neurodevelopmental deficits in neuronal migration and synaptic plasticity. However, our study group was small, and results should be verified using larger samples. Copyright (C) 2012 S. Karger AG, Basel

Microsurgical Anatomy of the Optic Radiation and Related Fibers in 3-Dimensional Images

BACKGROUND: The fiber dissection technique provides unique 3-dimensional anatomic knowledge of the white matter. OBJECTIVE: To examine the optic radiation anatomy and its important relationship with the temporal stem and to discuss its findings in relation to the approaches to temporal lobe lesions. METHODS: We studied 40 cerebral hemispheres of 20 brains that had been fixed in formalin solution for 40 days. After removal of the arachnoid membrane, the hemispheres were frozen, and the Klingler technique was used for dissection under magnification. Stereoscopic 3-dimensional images of the dissection were obtained for illustration. RESULTS: The optic radiations are located deep within the superior and middle temporal gyri, always above the inferior temporal sulcus. The mean distance between the cortical surface and the lateral edge of the optic radiation was 21 mm. Its fibers are divided into 3 bundles after their origin. The mean distance between the anterior tip of the temporal horn and the Meyer loop was 4.5 mm, between the temporal pole and the anterior border of the Meyer loop was 28.4 mm, and between the limen insulae and the Meyer loop was 10.7 mm. The mean distance between the lateral geniculate body and the lateral margin of the central bundle of the optic radiation was 17.4 mm. CONCLUSION: The white matter fiber dissection reveals the tridimensional intrinsic architecture of the brain, and its knowledge regarding the temporal lobe is particularly important for the neurosurgeon, mostly because of the complexity of the optic radiation and related fibers.

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 mu M CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFN gamma through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPAR gamma receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2 alpha, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2 alpha induced by LPS/IFN gamma. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ER stress pathway is involved in the 'oligoprotective' effects of CBD during inflammation. Cell Death and Disease (2012) 3, e331; doi:10.1038/cddis.2012.71; published online 28 June 2012

New structural brain imaging endophenotype in bipolar disorder

Neuroimaging studies suggest anterior-limbic structural brain abnormalities in patients with bipolar disorder (BD), but few studies have shown these abnormalities in unaffected but genetically liable family members. In this study, we report morphometric correlates of genetic risk for BD using voxel-based morphometry. In 35 BD type I (BD-I) patients, 20 unaffected first-degree relatives (UAR) of BD patients and 40 healthy control subjects underwent 3 T magnetic resonance scanner imaging. Preprocessing of images used DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry in SPM8 (Wellcome Department of Imaging Neuroscience, London, UK). The whole-brain analysis revealed that the gray matter (GM) volumes of the left anterior insula and right inferior frontal gyrus showed a significant main effect of diagnosis. Multiple comparison analysis showed that the BD-I patients and the UAR subjects had smaller left anterior insular GM volumes compared with the healthy subjects, the BD-I patients had smaller right inferior frontal gyrus compared with the healthy subjects. For white matter (WM) volumes, there was a significant main effect of diagnosis for medial frontal gyrus. The UAR subjects had smaller right medial frontal WM volumes compared with the healthy subjects. These findings suggest that morphometric brain abnormalities of the anterior-limbic neural substrate are associated with family history of BD, which may give insight into the pathophysiology of BD, and be a potential candidate as a morphological endophenotype of BD. Molecular Psychiatry (2012) 17, 412-420; doi: 10.1038/mp.2011.3; published online 15 February 2011

Biogeochemistry of an Amazonian podzol-ferralsol soil system with white kaolin

The podzol-ferralsol soil systems, which cover great areas of Amazonia and other equatorial regions, are frequently associated with kaolin deposits and store and export large amounts of carbon. Although natural organic matter (NOM) plays a key role in their dynamics, little is known about their biogeochemistry. In order to assess the specific role of dissolved organic matter (DOM) on NOM storage in deep horizons and to determine possible relationships between kaolin formation and DOM properties, we studied the groundwater composition of a typical podzol-ferralsol soil catena from the Alto Rio Negro region, Brazil. Groundwater was sampled using tension-free lysimeters placed according to soil morphology. DOC, E-H, p(H), and dissolved Si, Al3+, Fe2+, and Fe3+ were analyzed for all samples and values are given in a database. Quantification of other dissolved ions, small carboxylic acids and SUVA(254) index and acid-base microtitration was achieved on selected samples. Part of the DOM produced by the hydromorphic podzols is directly exported to the blackwater streams; another part percolates at greater depth, and more than 90% of it adsorbs in the Bh-Bhs horizons, allowing carbon storage at depth. Humic substances are preferentially adsorbed with regard to small carboxylic compounds. With regard to kaolin genesis, kaolinite precipitation is favored by Al release from NOM mineralization within the Bh-Bhs and kaolin bleaching is ensured by iron reduction due to acidity and relatively low E-H. Fe2+ mobility can be related to small E-H variations and enhanced by the significant concentration of small carboxylic acids. The long-term result of these processes is the thickening of the kaolin, and it can be inferred that kaolin is likely to occur where active, giant podzols are close to a slope gradient sufficient enough to lower the deep water table.

The nature of the companion of PSR J1719-1438: a white dwarf or an exotic object?

We raise the possibility that the very dense, compact companion of PSR J1719-1438, which has a Jupiter-like mass, is an exotic quark object rather than a light helium or carbon white dwarf. The exotic hypothesis naturally explains some of the observed features, and provides quite strong predictions for this system, to be confirmed or refuted in feasible future studies.

Cold-Nuclear-Matter Effects on Heavy-Quark Production in d+Au Collisions at root S-NN=200 GeV

The PHENIX experiment has measured electrons and positrons at midrapidity from the decays of hadrons containing charm and bottom quarks produced in d + Au and p + p collisions at root S-NN = 200 GeV in the transverse-momentum range 0.85 <= p(T)(e) <= 8.5 GeV/c. In central d + Au collisions, the nuclear modification factor R-dA at 1.5 < p(T) < 5 GeV/c displays evidence of enhancement of these electrons, relative to those produced in p + p collisions, and shows that the mass-dependent Cronin enhancement observed at the Relativistic Heavy Ion Collider extends to the heavy D meson family. A comparison with the neutral-pion data suggests that the difference in cold-nuclear-matter effects on light- and heavy-flavor mesons could contribute to the observed differences between the pi(0) and heavy-flavor-electron nuclear modification factors R-AA. DOI: 10.1103/PhysRevLett.109.242301

Influence of HSM cutting parameters on the surface integrity characteristics of hardened AISI H13 steel

The purpose of this study is to evaluate the influence of the cutting parameters of high-speed machining milling on the characteristics of the surface integrity of hardened AISI H13 steel. High-speed machining has been used intensively in the mold and dies industry. The cutting parameters used as input variables were cutting speed (v c), depth of cut (a p), working engagement (a e) and feed per tooth (f z ), while the output variables were three-dimensional (3D) workpiece roughness parameters, surface and cross section microhardness, residual stress and white layer thickness. The subsurface layers were examined by scanning electron and optical microscopy. Cross section hardness was measured with an instrumented microhardness tester. Residual stress was measured by the X-ray diffraction method. From a statistical standpoint (the main effects of the input parameters were evaluated by analysis of variance), working engagement (a e) was the cutting parameter that exerted the strongest effect on most of the 3D roughness parameters. Feed per tooth (f z ) was the most important cutting parameter in cavity formation. Cutting speed (v c) and depth of cut (a p) did not significantly affect the 3D roughness parameters. Cutting speed showed the strongest influence on residual stress, while depth of cut exerted the strongest effect on the formation of white layer and on the increase in surface hardness.