Home About us Contact
|
Home About us Contact | ||
|
|
||
Appearing White Matter (appearing + white_matter)
Kinds of Appearing White Matter Selected AbstractsMolecular Changes in Normal Appearing White Matter in Multiple Sclerosis are Characteristic of Neuroprotective Mechanisms Against Hypoxic InsultBRAIN PATHOLOGY, Issue 4 2003Ursula Graumann Multiple sclerosis is a chronic inflammatory disease of the CNS leading to focal destruction of myelin, still the earliest changes that lead to lesion formation are not known. We have studied the geneexpression pattern of 12 samples of normal appearing white matter from 10 post-mortem MS brains. Microarray analysis revealed upregulation of genes involved in maintenance of cellular homeostasis, and in neural protective mechanisms known to be induced upon ischemic preconditioning. This is best illustrated by the upregulation of the transcription factors such as HIF-1, and associated PI3K/Akt signalling pathways, as well as the upregulation of their target genes such as VEGF receptor 1. In addition, a general neuroprotective reaction against oxidative stress is suggested. These molecular changes might reflect an adaptation of cells to the chronic progressive pathophysiology of MS. Alternatively, they might also indicate the activation of neural protective mechanisms allowing preservation of cellular and functional properties of the CNS. Our data introduce novel concepts of the molecular pathogenesis of MS with ischemic preconditioning as a major mechanism for neuroprotection. An increased understanding of the underlying mechanisms may lead to the development of new more specific treatment to protect resident cells and thus minimize progressive oligondendrocyte and axonal loss. [source] Age-related white matter lesions are associated with reduction of the apparent diffusion coefficient in the cerebellumEUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2007P. Bugalho Cerebellar apparent diffusion coefficient (ADC) was found to be increased after acute cerebral hemispheric stroke. There are no data on cerebellar ADC changes in patients with chronic, age-related white matter lesions (ARWML). We aimed to determine longitudinal ADC variations on cerebral hemispheric and cerebellar white matter regions of patients with ARWML in order to study relations between ADC changes in both regions. ADC was measured serially (1-year interval) on lesioned periventricular frontal white matter, frontal and parietoccipital normal appearing white matter and middle cerebellar peduncles, on 19 aged patients with ARWML, which also underwent gait assessment. We compared regional ADC at 0 and 1 year and calculated variation percentages for each region. Correlation analysis was made between ADC variation in cerebellar regions and in contralateral hemispheric regions and between cerebellar ADC at 1 year and walking speed. After 1 year, ADC was higher on lesioned periventricular frontal white matter and lower on cerebellar regions. ADC variations on these regions were negatively correlated. Cerebellar ADC measured after 1 year was positively correlated with walking speed. This suggests a link between vascular disease progression inside frontal lesions and ADC reduction in contralateral cerebellar peduncles. Chronic ischemia in frontal white matter could have interrupted frontal-cerebellar circuits, producing hypometabolism in cerebellar regions (and worse performance on motor tasks), decreased perfusion and hence ADC reduction. [source] A Magnetization Transfer MRI Study of Deep Gray Matter Involvement in Multiple SclerosisJOURNAL OF NEUROIMAGING, Issue 4 2006Jitendra Sharma MD ABSTRACT Background/Purpose: Gray matter involvement in multiple sclerosis (MS) is of growing interest with respect to disease pathogenesis. Magnetization transfer imaging (MTI), an advanced MRI technique, is sensitive to disease in normal appearing white matter (NAWM) in patients with MS. Design/Methods: We tested if MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n= 60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio (MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm gapless slices covering the whole brain. Region-of-interest,derived MTR histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were obtained. Whole brain MTR was also measured. Results: Mean whole brain MTR and the peak position of the NAWM MTR histogram were lower in patients with MS than NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n= 10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or SP vs. NL. Conclusions: The MTI technique used in this cohort was relatively insensitive to disease in the deep gray matter nuclei despite showing sensitivity for whole brain disease in MS. It remains to be determined if other MRI techniques are more sensitive than MTI for detecting pathology in these areas. [source] Connexin 43 gap junction proteins are up-regulated in remyelinating spinal cordJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2007W.A. Roscoe Abstract Alterations in the expression of gap junction proteins have previously been observed in several diseases affecting the central nervous system; however, the status of connexin 43 (Cx43) has not yet been reported in spinal cord remyelination. We studied Cx43 expression in demyelination and remyelination by using a chronic guinea pig model of experimental allergic encephalomyelitis (EAE). Hartley guinea pigs were immunized with homogenized whole CNS and complete Freund's adjuvant. Animals became chronically ill by day 40 postimmunization, and animals with paralysis were entered into the study. Animals were treated on days 40,60 postimmunization with either saline or drugs that promote remyelination: an adenosine amine congener (100 ,g/kg), an anti-,4-integrin blocker (CT301; ELN 69299; 30 mg/kg), or a combination of both drugs. Remyelination was induced in all drug-treated groups. Cx43 expression was virtually absent in demyelinated lesions of saline-treated controls compared with healthy tissue and normal appearing white matter (P < 0.001), whereas Cx43 was considerably increased (300,500%) in remyelinating lesions of all treatment groups (P < 0.001), most notably in CT301-treated animals. These changes in Cx43 expression indicate that Cx43 may beimportant for recovery from neuroinflammation. © 2007 Wiley-Liss, Inc. [source] Quantitative MRI-pathology correlations of brain white matter lesions developing in a non-human primate model of multiple sclerosisNMR IN BIOMEDICINE, Issue 2 2007Erwin L. A. Blezer Abstract Experimental autoimmune encephalomyelitis (EAE) induced with recombinant human myelin/oligodendrocyte glycoprotein in the common marmoset is a useful preclinical model of multiple sclerosis in which white matter lesions can be well visualized with MRI. In this study we characterized lesion progression with quantitative in vivo MRI (4.7,T; T1 relaxation time,±,Gd-DTPA; T2 relaxation time; magnetization transfer ratio, MTR, imaging) and correlated end stage MRI presentation with quantitative ex vivo MRI (formaldehyde fixed brains; T1 and T2 relaxation times; MTR) and histology. The histopathological characterization included axonal density measurements and the numeric quantification of infiltrated macrophages expressing markers for early active [luxol fast blue (LFB) or migration inhibition factor-related protein-14 positive] or late active/inactive [periodic acid Schiff (PAS) positive] demyelinating lesion. MRI experiments were done every two weeks until the monkeys were sacrificed with severe EAE-related motor deficits. Compared with the normal appearing white matter, lesions showed an initial increase in T1 relaxation times, leakage of Gd-DTPA and decrease in MTR values. The progressive enlargement of lesions was associated with stabilized T1 values, while T2 initially increased and stabilized thereafter and MTR remained decreased. Gd-DTPA leakage was highly variable throughout the experiment. MRI characteristics of the cortex and (normal appearing) white matter did not change during the experiment. We observed that in vivo MTR values correlated positively with the number of early active (LFB+) and negatively with late active (PAS+) macrophages. Ex vivo MTR and relaxation times correlated positively with the number of PAS-positive macrophages. None of the investigated MRI parameters correlated with axonal density. Copyright © 2006 John Wiley & Sons, Ltd. [source] Axonal Pathology and Loss Precede Demyelination and Accompany Chronic Lesions in a Spontaneously Occurring Animal Model of Multiple SclerosisBRAIN PATHOLOGY, Issue 3 2010Frauke Seehusen Abstract Axonal damage has been highlighted recently as a cause of neurological disability in various demyelinating diseases, including multiple sclerosis, either as a primary pathological change or secondary due to myelin loss. To characterize and quantify axonal damage and loss in canine distemper demyelinating leukoencephalomyelitis (DL), formalin-fixed paraffin-embedded cerebella were investigated histochemically and immunohistochemically using the modified Bielschowsky's silver stain as well as antibodies against nonphosphorylated (n-NF), phosphorylated neurofilament (p-NF) and ,-amyloid precursor protein (,-APP). Injured axons characterized by immunoreactivity against n-NF and ,-APP were detected in early distemper lesions without demyelination. In subacute and chronic demyelinating lesions the number of injured axons increased. Moreover, a significant decrease in axonal density was observed within lesions and in the normal appearing white matter in DL as determined by morphometric analyses using Bielschowsky's silver stain and p-NF immunohistochemistry. Summarized, the observed findings indicate that axonal damage (i) occurs early in DL; (ii) can be detected before myelin loss; and (iii) represents a pivotal feature in advanced lesions. It must be postulated that axonal damage plays an important role in the initial phase as a primary event and during progression of nervous distemper as a result of demyelination. [source] Molecular Changes in Normal Appearing White Matter in Multiple Sclerosis are Characteristic of Neuroprotective Mechanisms Against Hypoxic InsultBRAIN PATHOLOGY, Issue 4 2003Ursula Graumann Multiple sclerosis is a chronic inflammatory disease of the CNS leading to focal destruction of myelin, still the earliest changes that lead to lesion formation are not known. We have studied the geneexpression pattern of 12 samples of normal appearing white matter from 10 post-mortem MS brains. Microarray analysis revealed upregulation of genes involved in maintenance of cellular homeostasis, and in neural protective mechanisms known to be induced upon ischemic preconditioning. This is best illustrated by the upregulation of the transcription factors such as HIF-1, and associated PI3K/Akt signalling pathways, as well as the upregulation of their target genes such as VEGF receptor 1. In addition, a general neuroprotective reaction against oxidative stress is suggested. These molecular changes might reflect an adaptation of cells to the chronic progressive pathophysiology of MS. Alternatively, they might also indicate the activation of neural protective mechanisms allowing preservation of cellular and functional properties of the CNS. Our data introduce novel concepts of the molecular pathogenesis of MS with ischemic preconditioning as a major mechanism for neuroprotection. An increased understanding of the underlying mechanisms may lead to the development of new more specific treatment to protect resident cells and thus minimize progressive oligondendrocyte and axonal loss. [source] | ||||||||||