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(
Reid, Welin, Wiberg, Terenghi, & Novikov, 2010
). Thus, a substantial
number of different molecules are activated by different mechanisms in neu-
rons after injury. They are all of importance for the survival of neurons and
particularly for redirection to the production of substances needed for nerve
regeneration (
Abe & Cavalli, 2008; Raivich & Makwana, 2007; Rossi,
Gianola, & Corvetti, 2007
).
The close interaction that normally occurs between axons and Schwann
cells is important for maintenance of the differentiation of the Schwann cells.
After injury, the Schwann cells are activated (or dedifferentiated) as a prep-
aration before proliferation. In the distal nerve segment, proteases in the
axons are rapidly activated for breakdown of the axon and both Schwann
cells and the invading and infiltrating macrophages contribute to the break-
down and ingestion of myelin. Myelin-associated genes in Schwann cells are
downregulated during this degeneration process. Other molecules, like neu-
ral cell adhesion molecule (NCAM), which is linked to non-myelinating
Schwann cells, are differently expressed depending on the relation to the
outgrowing axons (
Saito, Kanje, & Dahlin, 2010
). p-ERK1/2 and STAT3
expression is also lower in the distal nerve segment compared to just distal to
the site of transection, which may be related to the presence of inflammatory
cells or apoptotic Schwann cells. Schwann cells also rapidly express the tran-
scription factor ATF3 as a sign of activation after nerve injury, but such an
expression is downregulated in the distal nerve segment in the Schwann cells
along with the progress of the outgrowing axons (
Kataoka, Kanje, &Dahlin,
2007
). Again, these phenomena indicate that there is a close interaction
between the outgrowing axons and Schwann cells (
Fig. 7.1
).
During later phases of the nerve regeneration process, the myelination by
ensheathment of the outgrowing axons is promoted by positive regulators
between these axons and the different types of Schwann cells, which
includes a radial sorting process involving neuregulin-1 (
Jessen & Mirsky,
2008
). In addition to the role of ERK1/2, recent data also indicate that
the transcription factor Pax-3 has a role in differentiation and proliferation
of Schwann cells after a peripheral nerve injury (
Doddrell et al., 2012
).
Finally, and maybe of convincing importance, the transcription factor
c-Jun, which is expressed in Schwann cells, seems to be a global regulator
of theWallerian degeneration process, since it may determine the expression
of trophic factors, adhesion molecules, formation of regeneration tracks, and
myelin clearance as well as the control of distinct regenerative potential of
the peripheral nerve. If c-Jun is not induced, there is a dysfunction of repair
of the cell and with subsequent failure of functional recovery as well as
