Biology Reference
In-Depth Information
the obstacle for an efficient axonal outgrowth after delayed nerve repair or
reconstruction is the events that occur in the distal nerve segment. The
impaired axonal outgrowth after a delayed nerve repair or reconstruction
after a transection injury seems to be related to factors like a decrease in
p-ERK1/2 in Schwann cells in the distal nerve segment (
Tsuda,
Kanje, & Dahlin, 2011
). Furthermore, the number of Schwann cells that
express the transcription factor ATF3, which is also associated with an effi-
cient axonal outgrowth, declines with time after injury. This is particularly
obvious in experimental models if the delay exceeds 30 days with a resulting
impaired nerve regeneration (
Saito & Dahlin, 2008
). Apoptosis, detected by
the presence of cleaved caspase 3 in Schwann cells, increases substantially in
the distal nerve segment if the nerve repair or reconstruction is delayed
(
Tsuda et al., 2011
). Furthermore, the contact between the outgrowing
axons and the Schwann cells seems to be essential for the number of cells
that express cleaved caspase 3 only if the nerve repair is immediately per-
formed (
Tsuda et al., 2011
). A delayed nerve repair increases the number
of Schwann cells that express cleaved caspase 3 from around 10% of the cells
in the distal nerve segment up to around 20% after delayed nerve repair
irrespective of the length of the delay (
Saito et al., 2009
)(
Fig. 7.2
).
If a nerve injury is not repaired with 3 to 6 months, there is a substantial
decline in Schwann cell markers and an increase in fibrosis and proteoglycan
scar markers in the distal nerve segment (
Jonsson et al., 2013
). These changes
are similar to those reports that present a decrease in transcription factor, like
ATF3, overtime (
Saito &Dahlin, 2008
). Although it has been suggested that
a critical time point at which outcome of regeneration becomes poor appears
to be 3 months in experimental systems (
Jonsson et al., 2013
), even shorter
time, like 2 weeks, is sufficient to observe an impaired axonal outgrowth.
This phenomenon is related to both a less activation of Schwann cells and
an increased number of apoptotic cells (
Tsuda et al., 2011
).
The cell adhesion molecule NCAM is more abundant in the distal nerve
segment if an injured nerve trunk is repaired or reconstructed after a long
delay in experimental rat models. After the long delay, when the axonal out-
growth is particularly impaired, NCAM, which is associated with non-
myelinating Schwann cells, is predominantly seen in the distal nerve
segment. This indicates that particularly nonmyelinating Schwann cells
are present in the distal nerve segment if the nerve repair or reconstruction
is done with a delay (
Saito et al., 2009
). Therefore, the myelination of the
outgrowing axons may be severely impaired. c-Jun is probably critical in this
context, since it reprograms Schwann cells to generate a repair process in the
