Magnetic resonance imaging investigation of blood-brain barrier damage in adoptive transfer experimental autoimmune encephalomyelitis

Seeldrayers, Pierrette; Syha, Jutta; Morrissey, S. P.; Stodal, Horst; Vass, Karl; Jung, Stefan; Gneiting, T.; Lassmann, Hans; Haase, Axel; Hartung, Hans‐Peter; Toyka, Klaus V.

doi:10.1016/0165-5728(93)90250-3

Cited by 36 publications

(18 citation statements)

References 24 publications

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“…Accordingly, the macrophage inflammation marker MF I , which reflects whether macrophages in the lesions express markers of active or inactive lesions, showed the highest correlation with MTR. Both in EAE models and MS patients, the presence of inflammatory cells, and particularly macrophages, has been associated with a reduction in MTR (29,(34)(35)(36), but also with an increase in T 1 relaxation time [or decrease in T 1 -weighted intensity, the so called 'black holes' (35,37,38)] and mainly with the presence of Gd-DTPA enhancement (37)(38)(39)(40)(41)(42)(43). However most studies are descriptive and in only a few studies could quantitative MRI data be correlated with (semi-) quantitative histological data.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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 ; T 1 relaxation time AE Gd-DTPA; T 2 relaxation time; magnetization transfer ratio, MTR, imaging) and correlated end stage MRI presentation with quantitative ex vivo MRI (formaldehyde fixed brains; T 1 and T 2 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 T 1 relaxation times, leakage of Gd-DTPA and decrease in MTR values. The progressive enlargement of lesions was associated with stabilized T 1 values, while T 2 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 (LFBþ) and negatively with late active (PASþ) 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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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“…In the Lewis rat, lesions occur in the spinal cord, but not the cerebellum, during the first attack of EAE, whereas when EAE is reinduced lesions also occur in the cerebellum (Gordon et al, 2001). Recently, several papers using MRI techniques have reported that the permeability of the BBB in the brainstem and cerebellum increases early in the pathogenesis of ascending paralysis EAE (Floris et al, 2004, Rausch et al, 2003and Seeldrayers et al, 1993. Tonra et al (2001) found that, in SJL/J mice with PLP139-151-induced EAE, which develop ascending paralysis, disruption of the cerebellar BBB occurs prior to the disruption of the BBB in the spinal cord and the onset of clinical signs.…”

Section: Discussionmentioning

confidence: 99%

Blood–brain barrier disruption and lesion localisation in experimental autoimmune encephalomyelitis with predominant cerebellar and brainstem involvement

Muller

Pender

Greer

2005

Journal of Neuroimmunology

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The role of the blood-brain barrier (BBB) in determining lesion distribution was assessed in an atypical model of experimental autoimmune encephalomyelitis (EAE) induced in C3H/HeJ mice by immunisation with peptide 190-209 of myelin proteolipid protein, which can result in two distinct types of EAE, each with distinct lesion distribution. Areas of the BBB showing constitutively greater permeability in naïve mice did not correlate with the lesion distribution in EAE. BBB disruption occurred only in sites of inflammatory cell infiltration. Irrespective of the clinical type, the BBB was disrupted in the cerebellum and brainstem. Pertussis toxin had no effect on lesion distribution. Thus, lesion distribution is not influenced solely by BBB permeability.

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“…In general, however, linking a particular MRI feature to a specific pathology has been hampered by the simultaneous involvement of myelin and axonal structures and the presence of inflammatory cell infiltrates 29 as well as a focal and temporary breakdown of the blood-brain barrier (BBB). Animal studies showed that enhancing MRI lesions reflect a breakdown of the BBB 30,31 and are associated with macrophage activation. 32 In contrast, in the cuprizone model the observed MRI signal changes during cuprizone treatment most likely reflect an increase in the extracellular space due to depletion of myelin.…”

Section: Discussionmentioning

confidence: 99%

Multicontrast MRI of remyelination in the central nervous system

et al. 2005

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Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de-and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T 1 , T 2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination.

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Magnetic resonance imaging investigation of blood-brain barrier damage in adoptive transfer experimental autoimmune encephalomyelitis

Cited by 36 publications

References 24 publications

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

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

Blood–brain barrier disruption and lesion localisation in experimental autoimmune encephalomyelitis with predominant cerebellar and brainstem involvement

Multicontrast MRI of remyelination in the central nervous system

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