Craniofacial Muscles

11 Laryngeal Muscle Response to Neuromuscular Diseases and Speci fi c Pathologies
197
In addition to changes of MyHC isoforms as a function of denervation in ILMs,
other immunohistochemically identi fi ed factors have been discovered that impart
upon selected ILMs the capacity to resist nerve input loss and support repair. For
example, a recent report by Vega-Cordova et al. ( 2010 ) described changes to three
neurotrophic factors in the TA and PCA muscle following experimental denervation
of the RLN. Using immunohistochemistry to track the expression of brain-derived
neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin 4 (NT-4)
the investigators noted that neurotrophin expression in the TA and PCA responded
differentially to denervation over time. For the TA, NGF levels were initially
decreased, but rebounded after 6 weeks post-injury (Vega-Cordova et al. 2010 ) .
Both BDNF and NT-4 expression were unchanged 3 days following denervation
and 6 weeks post-injury in the TA. In contrast, the PCA demonstrated lower BDNF
level post-injury that never returned to pre-injury values. The PCA did not show any
differences in NGF or NT-4 expression levels at any point during the experiment.
A handful of reports suggest that TA muscle biology may differ signi fi cantly
from other forms of skeletal muscle in its inherent capacity to support reinnervation.
In typical skeletal muscle, denervation leads to atrophy and fi brosis, diminishing the
potential of the tissue to support reinnervation efforts (Kobayashi et al. 1997 ) . In
contrast, reports suggest that most laryngeal muscles, with the exception of the
PCA, are functionally and morphologically resistant to long-term loss of nerve
inputs (Johns et al. 2001 ; Morledge et al. 1973 ) , suggesting a greater potential for
recovery. In fact, a recent report by Miyamaru and colleagues has demonstrated that
the TA’s capacity to survive prolonged denervation may be due in part to the preservation
of optimal ratios of ACh receptors to nerve terminals. Preservation of ACh
receptors is an important prerequisite for robust reinnervation in skeletal muscle
tissue, since regenerating axonal sprouts target ACh receptors to re-establish effective
neuromotor communication (Miyamaru et al. 2008 ) . Subsequent reinnervation
of the TA by the RLN also has been demonstrated to effectively reverse denervationrelated
MyHC expression changes (up-regulation of type 2X and down-regulation
of type 2B isoforms) at the level of the whole muscle (Wu et al. 2004 ) . Considering
that denervation of the TA leads to the transition of one fast isoform (type 2B) to
another (type 2X), as noted above, it is not surprising that minimal functional
changes are noted in shortening velocities and contraction force (Johns et al. 2001 ;
Wu et al. 2004 ) . Together, these data support the conclusion that the TA is amenable
to re-innervation procedures and that the outcome of such procedures would likely
be quite ef fi cacious. Current work by Zealear and colleagues is testing these suppositions
through the development and use of implantable stimulators and electrotherapy
in canine models (Nomura et al. 2010 ; Zealear and Billante 2004 ; Zealear
et al. 2009 ).
Work by Shinners et al. ( 2006 ) has related the survivability of laryngeal muscles
after neurological insult to the distinctive remodeling capacity discussed above. The
authors identi fi ed heightened levels of fi ber remodeling immediately following
RLN nerve section that was maintained for 24 weeks post-injury. The authors concluded
that the remarkable regenerative capacities of the muscles may have facilitated
their ability to survive and regenerate following neurological insult. Regardless