Lipids and proteins in multiple sclerosis white matter.
TL;DR: Quantitative analyses of white matter from four brains of patients with multiple sclerosis and four control brains suggest that inadequacy of the fatty acid elongation process together with deficits of cerebrosides represent one of the early biochemical lesions in the white matter of the MS brain.
Abstract: — Quantitative analyses of white matter from four brains of patients with multiple sclerosis (MS) and four control brains were carried out for total and soluble proteins, individual lipid fractions, and their corresponding fatty acids. In three specimens from two of the MS brains there were reductions of cerebrosides and of the C20:1 acid in the ethanolamine glycerophosphatide (EGP) fraction and a slight increase of tetraenes and trienes, while all other components were present in concentrations similar to those in the controls. In three other samples from two of the MS brains, galactolipids were deficient to a greater extent than cholesterol, EGP or CGP (choline glycerophosphatide), while proteins were within the control range. In samples where thinning of myelin was observed in Luxol-blue stained sections, there were proportional decreases of all components. The percentage of C20:1 acid in the EGP fraction was reduced in two of three myelin preparations from corresponding samples of MS white matter, and that of C24:1 acid in the cerebroside fraction was reduced in all three MS myelin preparations when compared with the two controls. The data suggest that inadequacy of the fatty acid elongation process together with deficits of cerebrosides represent one of the early biochemical lesions in the white matter of the MS brain.
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01 Oct 1995
TL;DR: This edition has been revised to include new data on genetics, molecular biology, and the role of cellular structures on one side and the growing experience with MR patterns of less common myelin disorders on the other.
Abstract: This edition has been revised to include new data on genetics, molecular biology, and the role of cellular structures on one side and the growing experience with MR patterns of less common myelin disorders on the other. In addition, chapters have been added on disorders of which the white matter involvement was previously unclear.
414 citations
TL;DR: It is confirmed that there are alterations in the NAWM of MS patients and it is suggested that such changes might be relevant to the disability in MS.
Abstract: We attempted to define the role of subtle changes in the normal-appearing white matter (NAWM) in the development of disability in multiple sclerosis (MS). Twenty-seven clinically definite MS patients with either relapsing-remitting or chronic-progressive courses and 10 sex- and age-matched controls entered the study. For each patient and control, we studied two NAWM areas in the frontal lobe with magnetization transfer imaging (MTI). For patients, we also calculated the MT ratios (MTRs) for three contiguous areas of NAWM progressively further from "isolated" lesions visible on conventional MRI. Frontal NAWM in MS patients had lower mean MTRs than the frontal white matter of the controls (p = 0.02). MTRs in the NAWM adjacent to isolated lesions increased with distance from them to the cortical gray matter (p = 0.04). This pattern was typical for patients with chronic-progressive MS whose MTRs in the first two regions of NAWM adjacent to lesions were lower than those of the same regions of patients with relapsing-remitting MS. This study confirms that there are alterations in the NAWM of MS patients and suggests that such changes might be relevant to the disability in MS.
372 citations
TL;DR: The present study showed a significant elevation of the lysosomal enzyme beta-glucosaminidase in the microscopically normal white matter in MS as compared with controls, suggesting that the white matter may be rendered more susceptible to the pathogenetic process in this disease.
362 citations
TL;DR: Comparison of theory and experiment suggests that in a normal human brain, proteins, lipids, and non-heme iron provide comparable contributions to tissue phase contrast; however, the sign of iron and lipid contributions is opposite to theSign of contribution from proteins.
Abstract: Recently reported contrast in phase images of human and animal brains obtained with gradient-recalled echo MRI holds great promise for the in vivo study of biological tissue structure with substantially improved resolution. Herein we investigate the origins of this contrast and demonstrate that it depends on the tissue “magnetic architecture” at the subcellular and cellular levels. This architecture is mostly determined by the structural arrangements of proteins, lipids, non-heme tissue iron, deoxyhemoglobin, and their magnetic susceptibilities. Such magnetic environment affects/shifts magnetic resonance (MR) frequencies of the water molecules moving/diffusing in the tissue. A theoretical framework allowing quantitative evaluation of the corresponding frequency shifts is developed based on the introduced concept of a generalized Lorentzian approximation. It takes into account both tissue architecture and its orientation with respect to the external magnetic field. Theoretical results quantitatively explain frequency contrast between GM, WM, and CSF previously reported in motor cortex area, including the absence of the contrast between WM and CSF. Comparison of theory and experiment also suggests that in a normal human brain, proteins, lipids, and non-heme iron provide comparable contributions to tissue phase contrast; however, the sign of iron and lipid contributions is opposite to the sign of contribution from proteins. These effects of cellular composition and architecture are important for quantification of tissue microstructure based on MRI phase measurements. Also theory predicts the dependence of the signal phase on the orientation of WM fibers, holding promise as additional information for fiber tracking applications.
279 citations
Cites background from "Lipids and proteins in multiple scl..."
...Also in diseases such as stroke (22), Alzheimer’s (23, 24), and multiple sclerosis (25), the total concentration or the composition of the lipids, proteins, and iron may be quite different from that of the normal brain....
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TL;DR: Relapses tended to be less frequent and be significantly less severe and of shorter duration in the linoleate-supplemented group than in those receiving the oleate mixture, but clear evidence that treatment affected the overall rate of clinical deterioration was not obtained.
Abstract: Seventy-five patients in London and Belfast with multiple sclerosis were given daily supplements of a vegetable oil mixture containing either linoleate or oleate for two years in a double-blind control trial Relapses tended to be less frequent and were significantly less severe and of shorter duration in the linoleate-supplemented group than in those receiving the oleate mixture, but clear evidence that treatment affected the overall rate of clinical deterioration was not obtained
190 citations
References
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Journal Article•
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
TL;DR: In this article, the major lipids, including ethanolamine glycerophosphatides (EGP), serine glycephosphatide (SGP), choline glycephalophosphate (CGP), sphingomyelin, cerebroside, cerebrasides, and ceramide, were isolated from the frontal lobes of humans aged 10 months, 6 years, 9 years, and 55 years.
448 citations
315 citations
TL;DR: In this paper, a two-dimensional thin-layer chromatography (TLC) was developed that separated rat liver phosphatides into several phosphate-positive spots in about two hours developing time.
314 citations
TL;DR: Total protein and lipid content of myelin showed little variation, but lipid composition changed significantly during maturation, and cholesterol, galactolipids, and ethanolamine glycerophosphatide plasmalogen increased whereas choline glycerophile content decreased with increasing age.
Abstract: Myelin fractions were prepared from brains of 9- to 90-day-old rats by continuous and discontinuous sucrose density gradient procedures. Total protein and lipid content of myelin showed little variation, but lipid composition changed significantly during maturation. Cholesterol, galactolipids, and ethanolamine glycerophosphatide plasmalogen increased whereas choline glycerophosphatide content decreased with increasing age. The changes in lipid composition were more marked in the myelin prepared by the discontinuous gradient technique. The significance of these lipid changes in relation to their organization in the myelin membrane is discussed.
201 citations