Luxol Fast Blue (luxol + fast_blue)

Distribution by Scientific Domains

Selected Abstracts

Decreasing myelin density reflected increasing white matter pathology in Alzheimer's disease,a neuropathological study

Martin Sjöbeck
Abstract Background White matter disease (WMD) is frequently seen in Alzheimer's disease (AD) at neuropathological examination. It is defined as a subtotal tissue loss with a reduction of myelin, axons and oligodendrocytes as well as astrocytosis. Studies quantitatively defining the myelin loss in AD are scarce. The aim was to develop a method that could provide numerical values of myelin density in AD. The purpose was to compare the myelin contents in increasing grades of pathology of WMD, with age and cortical AD pathology as well as in different regions of the brain in AD. Material and methods Sixteen cases with AD and concomitant WMD were investigated with an in-house developed image analysis technique to determine the myelin attenuation with optical density (OD) in frontoparietal, parietal, temporal and occipital white matter on whole brain coronal sections stained for myelin with Luxol Fast Blue (LFB). The OD values in LFB were compared grouped according to Haematoxylin/Eosin (HE) evaluated mild, moderate and severe WMD or normal tissue. The OD values were also correlated with age and cortical AD pathology and compared between the different studied white matter regions. Results Increasing severity of WMD was associated with a statistically significant OD reduction. No correlation was seen between age and OD or overall cortical AD pathology. The OD values were significantly lower in frontoparietal-compared to occipital white matter. Conclusions Myelin loss in AD with WMD is a marked morphologic component of the disease and it is possible to determine the reduction objectively in neuropathological specimens with quantitative measures. This may be of use for clinical diagnostics including brain imaging. Copyright © 2005 John Wiley & Sons, Ltd. [source]

MRI identification of the rostral-caudal pattern of pathology within the corpus callosum in the cuprizone mouse model

Qi-Zhu Wu BS
Abstract Purpose To characterize and compare histological and MRI-based changes within the corpus callosum (CC) in the cuprizone mouse model of multiple sclerosis (MS). Materials and Methods A total of 12 C57/BL6 mice were fed cuprizone from eight weeks of age for four weeks. One cohort of six cuprizone and two control mice were scanned with a T2-weighted (T2W) sequence. The other cohort of six cuprizone and four control mice were scanned using a dual-echo sequence for T2-mapping and a diffusion-weighted sequence with two orthogonal diffusion encoding directions to calculate water diffusivities parallel and perpendicular to the CC fiber (apparent diffusion coefficients [ADC], and ADC,). After the mice were killed, the rostral-caudal pattern of CC demyelination and other pathologies were examined using Luxol Fast Blue, neurofilament staining, and immunohistochemistry for microglia and were correlated with MRI. Results In contrast to control mice, T2W imaging (T2WI) hyperintensity, reduced ADC,, and elevated ADC, were detected in the CC of cuprizone-fed mice, particularly in the caudal segment. The T2 value was increased in the entire CC. Marked demyelination, as well as axonal injury, microglia accumulation, and cellular infiltration were found in the caudal section of the cuprizone mouse CC. The rostral-caudal pattern of abnormalities within the CC in MRI measurements correlated well with histopathological findings. Conclusion Noninvasive MRI using quantitative T2 and ADC mapping accurately characterized the rostral-caudal pattern of CC demyelination and other pathologies in cuprizone challenged mice, and thus could provide an effective way to assess the structural response to experimental therapeutics being designed for the treatment of MS. J. Magn. Reson. Imaging 2007. © 2007 Wiley-Liss, Inc. [source]

Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelination

M. Lindner
To understand the mechanisms of remyelination and the reasons for regeneration failure is one of the major challenges in multiple sclerosis research. This requires a good knowledge and reliable analysis of experimental models. This work was undertaken to characterize the pattern of myelin protein expression during experimental remyelination. Acute demyelination of the corpus callosum was induced by feeding of 0.3% cuprizone for 6 weeks, followed by a 10-week remyelination period. We used a combination of Luxol fast blue (LFB) myelin staining, electron microscopy (EM) and immunohistochemistry for the myelin proteins 2,,3,-cyclic nucleotide 3, phosphodiesterase (CNPase), myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Early remyelination was detected by the re-expression of CNPase, MBP and PLP as early as 4 days. MOG, as a marker for late differentiation of oligodendrocytes, was not detectable until 2 weeks of remyelination. EM data correlated well with the LFB myelin staining and myelin protein expression, with 50% of the axons being rapidly remyelinated within 2 weeks. While particularly MBP but also PLP and CNPase are re-expressed very early before significant remyelination is observed by EM, the late marker MOG shows a lag behind the remyelination detected by EM. The presented data indicate that immunohistochemistry for various myelin proteins expressed early and late during myelin formation is a suitable and reliable method to follow remyelination in the cuprizone model. Furthermore, investigation of early remyelination confirms that the intrinsic repair programme is very fast and switched on within days. [source]

Remyelination can be extensive in multiple sclerosis despite a long disease course

R. Patani
Experimental studies using models of multiple sclerosis (MS) indicate that rapid and extensive remyelination of inflammatory demyelinated lesions is not only possible, but is the normal situation. The presence of completely remyelinated MS lesions has been noted in numerous studies and routine limited sampling of post mortem MS material suggests that remyelination may be extensive in the early stages but eventually fails. However, visual macroscopic guided sampling tends to be biased towards chronic demyelinated lesions. Here we have extensively sampled cerebral tissue from two MS cases to investigate the true extent of remyelination. Sections were cut from 185 cerebral tissue blocks and stained with haematoxylin and eosin (H&E), luxol fast blue and cresyl fast violet (LFB/CFV) and anti-myelin oligodendrocyte glycoprotein, human leucocyte antigen-DR (HLA-DR) and 200 kDa neurofilament protein antibodies. Demyelinated areas were identified in 141 blocks, comprising both white matter (WMLs) and/or grey matter lesions. In total, 168 WMLs were identified, 22% of which were shadow plaques, 73% were partially remyelinated and only 5% were completely demyelinated. The average extent of lesion remyelination for all WMLs investigated was 47%. Increased density of HLA-DR+ macrophages and microglia at the lesion border correlated significantly with more extensive remyelination. Results from this study of two patients with long standing disease suggest that remyelination in MS may be more extensive than previously thought. [source]

Quantitative MRI-pathology correlations of brain white matter lesions developing in a non-human primate model of multiple sclerosis

Erwin 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]