Biology Reference
In-Depth Information
factor (CNTF) receptor complex (
Tang et al., 2000
). Also, the expression of
many metabolic molecules, such as ferritin heavy chain, adhesion molecules,
such as N-CAM, and extracellular proteases, including urokinase, change in
response to muscle denervation. Finally, an increase in the level of ErbB2
and ErbB3 receptors and Neuregulin1 expression was also demonstrated
(
Ng, Pun, Yang, Ip, & Tsim, 1997; Nicolino et al., 2009; Suarez et al.,
2001
). These adaptive changes might act to maintain muscle fiber survival
during early stages of denervation and participate in the remodeling of
neuromuscular synapse (
Tang et al., 2000
).
Traditional strategies to improve motor functional recovery after injury
by delaying the effects of the denervation process include electrical stimu-
lation and rehabilitation of the denervated muscles (
Nicolaidis &
Williams, 2001
). These treatments can improve muscle function after nerve
injury in the clinical setting; however, they are not very effective in arresting
denervated muscle atrophy and patient compliance is often poor; moreover,
implantable electrical systems are expensive.
Microsurgical repair within 2 months of injury can essentially reverse
skeletal muscle changes and result in good functional recovery
(
Finkelstein, Dooley, & Luff, 1993
). In contrast, if surgery is delayed for
6 months or more, denervation results in irreversible structural damage,
including extrafusal fiber necrosis, connective tissue hyperplasia, and dete-
rioration of the muscle spindles, leading to poor reinnervation and func-
tional recovery (
Bain, Veltri, Chamberlain, & Fahnestock, 2001; Hynes,
Bain, Thoma, Veltri, & Maguire, 1997; Veltri et al., 2005
). Furthermore,
even when nerve surgery is performed early, there will still be a long period
of muscle denervation if the distance from the site of injury is substantial, and
the operative results are likely to be correspondingly poor.
A useful strategy to delay the skeletal muscle atrophy might be to connect
the end of a sensory nerve to the side of the distal nerve stump of the injured
nerve (sensory protection) in order to maintain the structural and functional
integrity of muscle until axons of the native nerve reach their target (
Bain
et al., 2001; Hynes et al., 1997; Irintchev et al., 1990; Veltri et al., 2005;
Wang, Gu, Xu, Shen, & Li, 2001
). This strategy uses a readily available sen-
sory nerve to directly or indirectly support denervated muscle fibers by the
supply of trophic factors, improve existing endoneurial sheath structure, and
enhance regeneration by the native nerve (
Veltri et al., 2005; Zhao et al.,
2004
). It has been shown that sensory protection minimizes two of the three
major structural consequences of chronic denervation: fiber necrosis and
connective tissue hyperplasia.
