Biology Reference
In-Depth Information
activated in a retrograde manner. The question remains open as to whether
doses of ESWT in the therapeutic range would induce similar changes as the
2000 impulses applied in this study. ATF-3 and GAP-43 are markers
thought to be associated with the activation of neurones and glial cells
(Schwann cells) after peripheral nerve injuries (
Hunt et al., 2004; Saito
and Dahlin, 2008
).
As regards the dose-effect relationship of ESWT on peripheral nerves, a
large body of evidence suggests that shock wave doses greater than 900
impulses combined with a flux density of 0.08 mJ/mm
2
induce damage
to the affected nerves, manifested in impaired electrophysiological conduc-
tion parameters (
Wu et al., 2007
), a disrupted neurofilament staining pattern
of the treated axons (
Hausner et al., 2012
), and degeneration of the myelin
sheaths at the levels of light and electron microscopy (
Bolt et al., 2004
).
These doses appeared to damage motor and sensory nerves equally (
Bolt
et al., 2004; Wu et al., 2007
). Our experimental and clinical experience indi-
cates that the therapeutically applicable dose for the promotion of nerve
regeneration without side effects is likely to be lower than 500 impulses
(0.1 mJ/mm
2
, 4 Hz) (
Hausner et al., 2012
). The effect of such doses is highly
dependent on the depth of the target tissue and the treated surface area.
4.2. Effects of ESWT on motor nerves
The question arose of whether doses of shock wave treatment that did not
cause degenerative events in the affected peripheral nerve segments would
foster the regeneration of injured axons in a rodent model. It was clearly
demonstrated that ESWT applied at a dose of 300 impulses and 0.1 mJ/
mm
2
did not induce the disintegration of neurofilaments within the axons
of the sciatic nerve (
Hausner et al., 2012
). The efficacy of this ESWT scheme
was tested in an autologous rat sciatic nerve model, where an 8-mm long
autograft was excised and coapted with the proximal and distal stumps.
When shock wave treatment was applied immediately after surgical recon-
struction, a significantly improved rate of axonal regeneration was observed
as early as 3 weeks after the injury. Not only were more regenerating axons
found in the reinnervated distal stump of the shock wave-treated nerves, but
also this early reinnervation was accompanied by moderate values of axon
conduction beyond the distal coaptation site. The morphological and func-
tional reinnervation of the denervated hind limb muscles could be expected
only at later time points. Functional tests revealed a clear improvement in the
ESWT animals from 4 weeks onward, but this difference in improved
