The objective of this study is to evaluate the activity of a novel peptide, i.e., bifunctional peptide inhibitor (BPI), which targets the immunological synapse and inhibits autoimmune responses in an antigen-specific manner. Proteolipid protein (PLP)-BPI was designed by conjugating two peptides, an encephalitogenic epitope of proteolipid protein (PLP(139-151)) and an intercellular adhesion mole...

I n this issue of The Journal of Experimental Medicine , Tuohy et al. study the spreading of the autoimmune response to myelin antigens in experimental autoimmune encephalo-myelitis (EAE) and its likely human counterpart, multiple sclerosis (MS) (1). They demonstrate that as disease develops in EAE and MS, reactivity to the initiating antigen diminishes , and an orderly and definable set of new...

To study the effects of naturally occurring growth hormone deficiency type I on CNS myelination, we compared the myelination of brains from little and wild-type littermate mice using molecular, histological, morphometric, and functional analyses. The little mouse produces only 6-8% of normal levels of growth hormone (GH) and approximately 20% of normal circulating levels of insulin-like growth ...

Extracellular matrix (ECM) proteins play a key role during oligodendrogenesis. While fibronectin (FN) is involved in the maintenance and proliferation of oligodendrocyte progenitor cells (OPCs), merosin (MN) promotes differentiation into oligodendrocytes (OLs). Mechanical properties of the ECM also seem to affect OL differentiation, hence this study aimed to clarify the impact of combined bioph...

During neonatal development glucocorticoids potentiate oligodendrocyte differentiation and myelinogenesis by regulating the expression of myelin basic protein, proteolipid protein, and glycerol phosphate dehydrogenase (sn-glycerol-3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8). The actual locus at which hydrocortisone exerts its developmental influence on glial physiology is, however, not well...

Multiple sclerosis is characterized by perivascular CNS infiltration of myelin-specific CD4(+) T cells and activated mononuclear cells. TCR transgenic mice on the SJL background specific for proteolipid protein (PLP)(139-151) develop a high incidence of spontaneous experimental autoimmune encephalomyelitis (sEAE). We examined the intrinsic mechanisms regulating onset and severity of sEAE. CD4(+...

BACKGROUND Progesterone as a sex steroid hormone is thought to affect and prevent demyelination, but its role in promoting myelin repair is far less investigated. In this study, remyelinating potential of progesterone in corpus callosum was evaluated on an experimental model of MS. METHODS In this experimental study, adult male C57BL/6 mice were fed with 0.2% (w/w) cuprizone in ground breeder...

BACKGROUND Neocortical lesions (NLs) are an important pathological component of multiple sclerosis (MS), but their visualization by magnetic resonance imaging (MRI) remains challenging. OBJECTIVES We aimed at assessing the sensitivity of multi echo gradient echo (ME-GRE) T2*-weighted MRI at 7.0 Tesla in depicting NLs compared to myelin and iron staining. METHODS Samples from two MS patients...

Axonal degeneration contributes to clinical disability in the acquired demyelinating disease multiple sclerosis. Axonal degeneration occurs during acute attacks, associated with inflammation, and during the chronic progressive phase of the disease in which inflammation is not prominent. To explore the importance of interactions between oligodendrocytes and axons in the CNS, we analysed the brai...