Biology Reference
In-Depth Information
reduce the ability of the patient to enjoy leisure activities and particularly
perform their work. Therefore, there is a high risk of long sick leave after
a peripheral nerve injury, and the costs for lost production may stand for
about 80% of the total cost for treatment (
Rosberg et al., 2005; Thorsen,
Rosberg, Steen Carlsson, & Dahlin, 2012
). The final outcome of a nerve
injury depends on many factors. The individual surgeon cannot affect the
majority of them, but the time at which a nerve injury should be repaired
or reconstructed is important. A patient with a trauma to the hand, arm,
shoulder, or lower leg should be properly examined in the emergency room
with the attempt to make an appropriate diagnosis of any nerve injury. Once
the diagnosis of a nerve injury has been made, all efforts should be directed to
repair or reconstruct the nerve injury as soon as possible, although one
should consider the general condition of the patient, that is, strict medical
priority of the patient's injuries. Based on the delicate intracellular signaling
pathways that are rapidly initiated in neurons and non-neuronal cells with
the purpose to induce regeneration as well as recent advances in the knowl-
edge about brain plasticity in rehabilitation strategies, the factor
timing
of
nerve repair and reconstruction will be the key word.
1. THE INTRINSIC RESPONSE IN NEURONS AND
SCHWANN CELLS AFTER INJURY
After a nerve transection, signals are initiated and sent from the site of
injury along the proximal segment of the transected axon up to the nerve cell
body (
Fig. 7.1
). These signals may be both positive and negative in nature.
The normally transported retrograde signals from targets or from the micro-
environment of the axon may be suppressed by the inhibition of axonal
transport of substances from the periphery, that is, a negative injury signal.
The transcription factor, nuclear factor kappa B, bears a specific code, which
is called a nuclear localization sequence, and allows the entrance in the
nucleus. Trauma to the nerve may inactivate this factor and thereby it is also
an important negative modulator of the response in the nerve cell body
(
Raivich &Makwana, 2007
). After transection, the proximal tip of the axon
is rapidly sealed after extracellular cations, such as Na
þ
and Ca
2
þ
, are diffused
through the open cell membrane. The entrance of calcium is also reported to
be important for local activation of protein kinases at the tip of the axons.
One example of such a locally activated protein kinases is extracellular
signal-regulated kinase (ERK) that is fundamental for activation both in
neurons and in Schwann cells (
M
˚
rtensson, Gustavsson, Dahlin, & Kanje,
