Degeneration of phrenic motor neurons induces long-term diaphragm deficits following
mid-cervical spinal contusion in mice
-
1
Universite Libre de Bruxelles, Laboratoire d'histologie, de neuroanatomie et de neuropathologie, Belgium
-
2
Thomas Jefferson University, Department of Neuroscience, United States
-
3
Arcadia University, United States
A primary cause of morbidity and mortality following cervical spinal cord injury (SCI) is
respiratory compromise, regardless of the level of trauma. In particular, SCI at mid-cervical
regions targets degeneration of both descending bulbospinal respiratory axons and cell bodies of
phrenic motor neurons, resulting in deficits in the function of the diaphragm, the primary muscle
of inspiration. Contusion-type trauma to cervical spinal cord is one of the most common forms of
human SCI; however, few studies have evaluated mid-cervical contusion in animal models or
characterized consequent histopathological and functional effects of degeneration of phrenic
motor neuron-diaphragm circuitry. We have generated a mouse model of cervical contusion SCI
that unilaterally targets both C4 and C5 levels, the location of the phrenic motor neuron pool, and
have examined histological and functional outcomes for up to 6 weeks post-injury. We report
that phrenic motor neuron loss in cervical spinal cord, phrenic nerve axonal degeneration, and
denervation at diaphragm neuromuscular junctions resulted in compromised ipsilateral
diaphragm function, as demonstrated by persistent reduction in diaphragm compound muscle
action potential amplitudes following phrenic nerve stimulation and abnormalities in
spontaneous diaphragm EMG recordings. This injury paradigm is reproducible, does not require
ventilatory assistance and provides proof-of-principle that generation of unilateral cervical
contusion is a feasible strategy for modeling diaphragmatic/respiratory deficits in mice. This
study and its accompanying analyses pave the way for using transgenic mouse technology to
explore the function of specific genes in pathophysiology of phrenic motor neuron degeneration
and respiratory dysfunction following cervical SCI.
Acknowledgements
This work was supported by the Université Libre de Bruxelles (Bureau des Relations
Internationales et de la Coopération, grant BRIC-11/092 to C.N.), the Craig Nielsen Foundation
(grant #190140 to A.C.L.) and the Paralyzed Veterans of America (grant #160837 to A.C.L.).
We are grateful to Michele Authelet and Ricardo Nieves for technical assistance. We thank Dr.
Warren Alilain for helpful discussion regarding EMG data. We thank Aileen Anderson and
Rebecca Nishi for valuable advice in setting up th
Keywords:
cervical contusion,
phrenic motor neuron,
Respiration,
spinal cord injury
Conference:
Belgian Brain Council, Liège, Belgium, 27 Oct - 27 Oct, 2012.
Presentation Type:
Poster Presentation
Topic:
Higher Brain Functions in health and disease: cognition and memory
Citation:
Nicaise
C,
Putatunda
R,
Hala
TJ,
Regan
KA,
Frank
DM,
Brion
J,
Leroy
K,
Pochet
R,
Wright
MC and
Lepore
AC
(2012). Degeneration of phrenic motor neurons induces long-term diaphragm deficits following
mid-cervical spinal contusion in mice.
Conference Abstract:
Belgian Brain Council.
doi: 10.3389/conf.fnhum.2012.210.00135
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Received:
20 Apr 2012;
Published Online:
12 Sep 2012.
*
Correspondence:
Dr. Charles Nicaise, Universite Libre de Bruxelles, Laboratoire d'histologie, de neuroanatomie et de neuropathologie, Bruxelles, 1070, Belgium, charles.nicaise@unamur.be