Biology Reference
In-Depth Information
treatment had demonstrated regeneration-promoting potential before
(
Haastert, Lipokatic, Fischer, Timmer, & Grothe, 2006; Haastert, Ying,
Grothe, & Gomez-Pinilla, 2008
). Electrical stimulation plus transplantation
of na¨ve Schwann cells increased the regeneration of gap-bridging nerve tis-
sue in comparison to nerve reconstruction with cell-free tubes. Unexpect-
edly, no further increase of macroscopic tissue regeneration after
transplantation of FGF-2 overexpressing Schwann cells was found. How-
ever, electrical stimulation combined with the chosen gene therapy para-
digm resulted in a high rate of regenerated nerves that functionally
reconnected to the target muscle (
Haastert-Talini et al., 2011
).
Combination of electrical stimulation with a gene therapy approach was
also tested by another group. After sciatic nerve crush injury, either electrical
stimulation or adenoviral brain-derived neurotrophic factor (BDNF) gene
therapy was applied and compared to a combined treatment (
Alrashdan
et al., 2011
). In comparison to no treatment, either electrical stimulation
or BDNF supplementation alone resulted in an increase of axonal regener-
ation but the combination of both eliminated the positive effects (
Alrashdan
et al., 2011
). The study again revealed that combinatory treatments have to
be carefully adjusted to each other to allow synergistic effects.
Moderate-intensity treadmill training as another treatment shown to
increase axonal and functional recovery has also been combined with acute
brief electrical stimulation in a model of sciatic nerve transection and suture
(
Asensio-Pinilla et al., 2009
). Those treatment strategies synergistically
supported the regeneration processes by shortening the period of staggered
axonal outgrowth and maintaining regeneration-supportive stimuli medi-
ated from the target tissue (
Asensio-Pinilla et al., 2009
). While in the initial
study, the accelerated recovery of nociception and muscle reinnervation was
recognized as a positive outcome of the study (
Asensio-Pinilla et al., 2009
),
especially the effect of the combined treatment on the development of neu-
ropathic pain was investigated in a recent study (
Cobianchi, Casals-Diaz,
Jaramillo, & Navarro, 2013
). The development of neuropathic pain is a sign
of maladaptation of nociceptors during regeneration-related plastic changes
and can be modulated if excessive sprouting of sensory fibers is limited
(
Cobianchi et al., 2013
). Acute electrical stimulation followed by high-
intensity short-term treadmill training has been shown to be effective to
avoid development of neuropathic pain (
Cobianchi et al., 2013
). The
regeneration-promoting effects of both treatments are neurotrophin depen-
dent and the signal cascades seem to be balanced to provide synergistic sup-
port of functional recovery (
Cobianchi et al., 2013
).
