Steps in the Pathogenesis of Multiple Sclerosis - I: From Neuroinflammation to Neurodegeneration

Abstract

Steps in the Pathogenesis of Multiple Sclerosis - I: From

Neuroinflammation to Neurodegeneration

Background: Inflammation has been described as a deleterious factor

in MS immunopathogenesis for a long time. However, recent studies

have proved the neuronal protective and efficacious effects of

inflammation. Inflammation in the brain is a double-edged process that

may be beneficial in promoting homeostasis and repair, but can also

result in tissue injury through the damaging potential of inflammatory

mediators. Control mechanisms that minimize the extent of the

inflammatory reaction are necessary in order to preserve brain

architecture and restore function. The end result of the inflammatory

process, neurotoxicity and/or neuroprotection, is a function of the fine

balance between the two cellular systems and of the complex signaling

relationships between anti-inflammatory neuroprotective factors. In

central nervous system inflammation the extent of tissue injury

depends on both native and adaptive elements of the immune system.

Besides, inflammation is not limited with the invasion of exogeneus cells

infiltrating from the blood brain barrier. Astrocytes and microglial cells

as being endogeneous also play an important role in the process.

Secondary inflammatory mediators from these cells trigger the unique

local inflammation of central nervous system. In the active MS plaques

distinct cytokines and chemokines have been determined.

C o n c l u s i o n: Inflammation has different aspects and some proof of

beneficial roles can be summarized: Before the clinical signs of /during the

experimental allergic encephalomyelitis (EAE) the presence of IFN-g h a s

been shown as a limitting factor for the progression, the delivery of anti-

I F N -g monoclonal antibodies have increased the morbidity in EAE. CD4+ T

cells stimulate microglial cells to secrete some mediators as interleukin E2

that can supress IL-12 and the same cells can also secrete neruprotective

factors as brain derived neurotrophic factor. Another group of cells,

macrophages trigger remyelinization by clearing myelin debris.

This review discusses about the contradictory effects of inflammation on

the immunopathogenesis of multiple sclerosis. It outlines the cells

responsible for the inflammatory cascade, both beneficial and

detrimental effects of inflammation on myelin and axonal integrity and

additional relation for demyelination and axonal transsection.