http://www.jneurosci.org/content/22/8/3052.short
Full 9 pages at the link.
Abstract
Wallerian degeneration (WD) is the
inflammatory response of the nervous system to axonal injury, primarily
attributable to
the production of cytokines, the mediator
molecules of inflammation. We presently document the involvement of the
inflammatory
cytokines TNFα, interleukin (IL)-1α, and IL-1β
in peripheral nerve (PNS) injury in C57/BL/6NHSD (C57/BL) mice that
display
the normal rapid progression of WD (rapid-WD)
and C57/BL/6-WLD/OLA/NHSD mice that display abnormal slow progression of
WD
(slow-WD). TNFα and IL-1α mRNAs were expressed,
whereas TNFα but not IL-1α protein was synthesized in intact PNS of
C57/BL
mice. TNFα and IL-1α protein synthesis and
secretion were rapidly upregulated during rapid-WD in Schwann cells.
IL-1β mRNA
expression and protein synthesis and secretion
were induced sequentially in Schwann cells with a delay after injury.
Thereafter,
recruited macrophages contributed to the
production of TNFα, IL-1α, and IL-1β, which in turn augmented myelin
phagocytosis
by macrophages. Observations suggest that TNFα
and IL-1α are the first cytokines with protein production that is
upregulated
during rapid-WD. TNFα and IL-1α may initiate,
therefore, molecular and cellular events in rapid-WD (e.g., the
production of
additional cytokines and NGF). TNFα, IL-1α, and
IL-1β may further regulate, indirectly, macrophage recruitment, myelin
removal,
regeneration, and neuropathic pain. In contrast
to rapid-WD, the production of TNFα, IL-1α, and IL-1β protein was
deficient
in slow-WD, although their mRNAs were expressed.
mRNA expression and protein production of TNFα, IL-1α, and IL-1β were
differentially
regulated during rapid-WD and slow-WD,
suggesting that mRNA expression, by itself, is no indication of the
functional involvement
of cytokines in WD.
Thanks Dean!! This is pretty technical but, I think it's explaining why my one and two year MRIs show "early" wd. I had wondered and asked the doctors why it was early nearly 2years later. The research I found said that WD is associated with worse outcomes...so I just feel lucky to be as good as I am. :-)
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