Biology Reference
In-Depth Information
on measures of isometric force of the reinnervated extensor digitorum
longus muscle (
Pachter & Eberstein, 1989
). More recently, the effects of pas-
sive exercise have been extensively explored in the rat model of the pure
motor facial nerve transection and direct suture (
Angelov et al., 2007;
Evgenieva et al., 2008; Guntinas-Lichius et al., 2007; Pavlov et al., 2008;
Sohnchen et al., 2010
; reviewed in
Skouras, Ozsoy, Sarikcioglu, &
Angelov, 2011
). Though applied daily for just few minutes, manual stimu-
lation of facial muscles restored whisking function in the latter nerve injury
model (
Angelov et al., 2007
). Similar positive outcome of passive manual
stimulation is achieved following injury of the hypoglossal nerve
(
Evgenieva et al., 2008
), and in both cranial nerves, enhanced functional
recovery is linked to reduced polyinnervation of motor end plates within
the target muscles (
Angelov et al., 2007; Evgenieva et al., 2008
).
Recovery of whisking function by manual stimulation requires integrity
of the trigeminal nerve (
Pavlov et al., 2008
). Therefore, increased descen-
dent synaptic input and firing of facial nerve motoneurons as a consequence
of manual stimulation seem to support whisking function recovery. How-
ever, the role of manual stimulation in promoting whisking function recov-
ery and reducing the amount of muscle end plate polyinnervation relies on
both IGF-1 (
Kiryakova et al., 2010
) and BDNF and its trkB receptor
(
Sohnchen et al., 2010
). Unlike wild-type mice, heterozygous IGF-1-
deficient mice fail to respond favorably to manual stimulation following
facial nerve transection and repair, both in the extent of whisking function
recovery and in the amount of muscle end plate polyinnervation (
Kiryakova
et al., 2010
). A number of studies confirm that IGF-1 plays a key role in PNS
regeneration (
Kim, Leventhal, Saltiel, & Feldman, 1997
; reviewed in
Sullivan, Kim, & Feldman, 2008
). Expression of IGF-1 and IGF-2, that
occurs in motoneurons (
Sullivan et al., 2008
), Schwann cells (
Cheng
et al., 1996
), macrophages, and muscle, is neuroprotective and supports
nerve regeneration after sciatic nerve injury (
Kanje, Skottner, Sjo¨berg, &
Lundborg, 1989
), while neutralization of IGF-1 slows down nerve regen-
eration (
Glazner, Morrison, & Ishii, 1994; Streppel et al., 2002
). Also,
IGF-1 enhances neurite outgrowth in cultured motoneurons and encour-
ages axonal sprouting in paralyzed muscles (
Caroni, Schneider, Kiefer, &
Zapf, 1994
). Since normal IGF-1 expression is required for manual stimu-
lation efficacy, it is reasonable to suggest that manual stimulation raises
IGF-1 levels in the regenerating facial nerve and possibly also in reinnervated
muscles. In this respect, IGF-1 levels in cultured myoblasts decay by
