CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation.

Perivascular macrophages (PVM) constitute a subpopulation of resident macrophages in the central nervous system (CNS) that by virtue of their strategic location at the blood-brain barrier potentially lend themselves to a variety of important functions in both health and disease. Functional evidence suggests that PVM play a supportive role during experimental autoimmune encephalomyelitis in rodents. However, the function of PVM in the human CNS remains poorly characterized.

Determination of the sequential degradation of myelin proteins by macrophages.

Demonstration of different myelin proteins (myelin basic protein [MBP], proteolipid protein [PLP] and myelin oligodendrocyte glycoprotein [MOG]) is used as a tool to determine the stage of MS lesions in autopsy tissue. Since such tissue can never be obtained at well-defined stages of lesion formation, the time course of myelin degradation in MS lesions can only be estimated. In order to obtain a more precise indication on the sequence of events of myelin degradation in MS lesions, the breakdown of human myelin by human monocytes was studied in vitro.

Multiple sclerosis as a generalized CNS disease--comparative microarray analysis of normal appearing white matter and lesions in secondary progressive MS.

We used microarrays to compare the gene expression profile in active lesions and donor-matched normal appearing white matter (NAWM) from brain autopsy samples of patients with secondary progressive multiple sclerosis (MS) with that from controls who died from non-neurological diseases. The 123 genes in lesions, and 47 genes in NAWM(MS) were differentially expressed. Lesions distinguished from NAWM(MS) by a higher expression of genes related to immunoglobulin synthesis and neuroglial differentiation, while cellular immune response elements were equally dysregulated in both tissue compartments.

Role of IDO activation in anti-microbial defense in human native astrocytes.

The most serious complication of human toxoplasmosis is the development of toxoplasmic encephalitis. It is well established that in the brain Toxoplasma gondii is able to replicate in microglial cells, astrocytes and neurons, and that all three cell types can harbor toxoplasma cysts. The role of astrocytes in the defense against toxoplasma is not clear.

CX3CL1 and CX3CR1 expression in human brain tissue: noninflammatory control versus multiple sclerosis.

An important role for CX3CL1 in neuroinflammation and neurodegeneration has been suggested in recent publications. In this study, we compared the expression of CX3CL1 and its receptor CX3CR1 in human brain tissue derived from control patients without neurological complications and in multiple sclerosis (MS) patients. Results from this study demonstrate that CX3CL1 is constitutively expressed in human central nervous system (CNS) astrocytes in vivo and under basal conditions in human adult astrocyte cultures.

Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance.

Background: Various types of pathologic mechanisms in multiple sclerosis (MS) can alter magnetic resonance imaging (MRI) signals, and the appearance of remyelinated lesions on MRI is largely unknown.

Objective: To describe the MRI appearance of remyelinated lesions in MS.

Design: Comparison of postmortem MRI findings with histopathologic findings.

Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions.

Matrix metalloproteinases (MMPs) are proteases involved in extracellular matrix (ECM) remodeling, leukocyte infiltration into lesions and myelin degradation in the central nervous system (CNS) disease multiple sclerosis (MS). We have investigated whether MMP-12 (macrophage metalloelastase) is expressed in MS lesions at various stages. In control patient tissue and (p)reactive MS lesions, only occasional microglial and astrocyte staining was detected.

Cellular localization and expression patterns of interleukin-10, interleukin-4, and their receptors in multiple sclerosis lesions.

Cytokines have been shown to play a crucial role in the pathogenesis of multiple sclerosis (MS). However, still limited data are available on the expression of anti-inflammatory cytokines within the central nervous system (CNS) during MS lesion development. Therefore, we have examined the expression of the anti-inflammatory cytokines, interleukin-10 (IL-10) and IL-4, and their specific receptors, IL-10R and IL-4R, in postmortem human brain tissue obtained from MS patients.

Beneficial effect of modified peptide inhibitor of alpha4 integrins on experimental allergic encephalomyelitis in Lewis rats.

An important event in the pathogenesis of the autoimmune disease multiple sclerosis (MS) is the recruitment of lymphocytes and inflammatory macrophages to the central nervous system (CNS). Recruitment requires adhesive interactions between the leukocytes and the microvascular endothelium, perivascular cells, and astrocytes in the CNS parenchyma. Previous studies using an animal model of MS, experimental allergic encephalomyelitis (EAE), have shown the involvement of the alpha4 integrin VLA-4 (beta4beta1).