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In-Depth Information
The mechanisms underlying the regeneration-promoting effect of elec-
trical stimulation are subject of the following section.
3. BIOLOGICAL EFFECTS OF ELECTRICAL STIMULATION
OF INJURED PERIPHERAL NERVES
3.1. General effect on axonal regeneration
The period of staggered axonal regeneration is significantly shortened
( Al-Majed, Neumann, et al., 2000 ), but not the speed of axonal elongation
( Brushart et al., 2002 ). Furthermore, the correct reinnervation of axonal
motor and sensory pathways is supported by brief electrical stimulation
( Al-Majed, Neumann, et al., 2000; Brushart, Jari, Verge, Rohde, &
Gordon, 2005 ). The positive effect on correct muscle reinnervation can
be further triggered with muscle-derived signals initiated by treadmill exer-
cise ( Asensio-Pinilla et al., 2009 ).
The electrical treatment is accelerating the number of axons crossing the
nerve repair site as a function of time, but it is not accelerating axonal trans-
port mechanisms or the speed of axonal elongation within the distal nerve
stump ( Gordon, Brushart, & Chan, 2008 ).
Electrical stimulation applied in nerve gap repair also accelerates
regrowth of nerve tissue into nerve guidance channels and anticipates mat-
uration and myelination of regenerated axons ( Haastert-Talini et al., 2011;
Singh et al., 2012 ). When combined with silicone tube repair of short nerve
gaps in mice ( Singh et al., 2012 ) or lengthy nerve gaps with autotransplants
in rats ( Haastert-Talini et al., 2011 ), electrical stimulation does not only
improve motor recovery but also anticipates sensory recovery. Furthermore,
as mentioned above, earlier reinnervation of sensory targets by electrical
stimulation has recently been linked to reduced development of neuropathic
pain after peripheral nerve injury ( Cobianchi et al., 2013 ).
Incomplete functional recovery is not only attributed to impeded axonal
regeneration but also to the misdirection of axons into inappropriate motor
targets, for example, antagonist muscles ( Valero-Cabre & Navarro, 2002 ).
Whether electrical stimulation can positively influence the reinnervation of
appropriate motor targets was addressed in a model of selective prestimulation
of a single sciatic nerve branch prior to transection of the complete nerve trunk
at mid-thigh level ( Hamilton et al., 2011 ). Interestingly, electrical
prestimulation did not reduce but increase misdirection of regenerating motor
axons into inappropriate motor targets ( Hamilton et al., 2011 ). This finding
not only strengthens again the outgrowth-promoting effect of electrical
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