Biology Reference
In-Depth Information
Recently, it has been demonstrated that the neuronal expression of not
only BDNF but also additional neurotrophic factors is increased after elec-
trical stimulation
in vivo
. In the ventral horn Neurotrophin-3 and in the dor-
sal root ganglia nerve growth factor (NGF) and glia-derived neurotrophic
factor showed significant upregulation after acute electrical stimulation
(
Cobianchi et al., 2013
).
The optimal orchestration of the neurotrophin-dependent signals not
only in neurons but also in Schwann cells finally leads to successful nerve
regeneration.
3.3. Impact of electrical stimulation on Schwann cells
Electrical stimulation, when applied directly to the nerve at levels proximal
to the nerve suture, is sufficient to increase neurotrophic factor levels in the
distal nerve as well (
Wang et al., 2009
). Partly, the increased amount of neu-
rotrophic factors is of neural origin and subsequently stimulates the biolog-
ical activity of Schwann cells in the distal nerve (
Wang et al., 2009
).
As downstream effector of neurotrophin signaling in Schwann cells of
motor pathways, the HNK-1 carbohydrate has been discussed. Its expression
has been shown to contribute to the preferential motor reinnervation
(PMR) phenomenon in the femoral nerve model, and this specific expres-
sion pattern is significantly enhanced by short-term electrical stimulation of
acutely injured and reconnected nerves (
Eberhardt et al., 2006
). Again, the
importance
of BDNF signaling for the translation of electrical stimulation
into increased axonal regeneration has been evidenced by the abolishment
of increased HNK-1 expression after electrical stimulation in the distal nerve
stump in trkB-deficient mice (
Eberhardt et al., 2006
).
With regard to PMR, it is of high importance to recognize that the guiding
Schwann cells and regenerating axons can influence each other reciprocally.
Polysialic acid (PSA) linked to the neural cell-adhesion molecule (NCAM)
has been shown to crucially contribute to the PMR phenomenon (
Franz,
Rutishauser, &Rafuse, 2005
). Subsets of femoral motoneurons, which regen-
erate preferentially into the motor branch instead of the sensory branch of the
femoral nerve, show an upregulation of PSA-NCAM (
Franz et al., 2005
).
Electrical stimulation increases the upregulation of PSA and thereby further
improves preferential motor axonal regeneration into motor target tissue
(
Franz, Rutishauser, & Rafuse, 2008
). However, it has to be remembered
that if appropriate and inappropriate motor targets are located distal to the
lesioned nerve, electrical stimulation does not positively influence appropriate
reinnervation of original motor targets (
Hamilton et al., 2011
).
