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

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.