Name: a murine model of cervical spinal cord injury to study post-lesional respiratory neuroplasticity
Uploaded: 2014-05-28T13:00:00
Description: Watch this Scientific Journal Video about A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity Video at JoVE.com

This work is supported by funding from the European Union Seventh framework Programme (FP7/2007-2013) under grant agreement No. 246556 (European project RBUCE-UP), HandiMedEx allocated by the French Public Investment Board.&#160;Marcel Bonay was supported by the Chancellerie des Universit&#233;s de Paris (Legs Poix), the Fonds de Dotation Recherche en Sant&#233; Respiratoire, and the Centre d&#8217;Assistance Respiratoire &#224; Domicile d&#8217;&#206;le de France (CARDIF)

This protocol was approved by the Ethics committee of the RBUCE-UP chair of Excellence (University of Paris Sud, grant agreement No. 246556) and the Universit&#233; de Versailles Saint-Quentin-en-Yvelines.
1. Preparation of Sterilized Surgical Instruments
<ol>
	<li>Clean the surgical instruments with laboratory detergent.</li>
	<li>Autoclave the instruments prior to surgery.</li>
	<li>In a surgical session, sterilize the tools by placing the tips in a hot bead sterilizer for 10 min at 180 &#...

<ol>
	<li>Frankel, H. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Long-term+survival+in+spinal+cord+injury:+a+fifty+year+investigation.">Long-term survival in spinal cord injury: a fifty year investigation.</a> Spinal Cord. 36, 266-274 (1998).</li><li>Ramer, M. S., Harper, G. P., Bradbury, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progress+in+spinal+cord+research+-+a+refined+strategy+for+the+International+Spinal+Research+Trust.">Progress in spinal cord research - a refined strategy for the International Spinal Research Trust.</a> Spinal Cord. 38, 449-472 (2000).</li><li>Zimmer, M. B., Nantwi, K., Goshgarian, H. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+spinal+cord+injury+on+the+respiratory+system:+basic+research+and+current+clinical+treatment+options.">Effect of spinal cord injury on the respiratory system: basic research and current clinical treatment options.</a> J Spinal Cord Med. 30, 319-330 (2007).</li><li>Mantilla, C. B., Sieck, G. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromuscular+adaptations+to+respiratory+muscle+inactivity.">Neuromuscular adaptations to respiratory muscle inactivity.</a> Respir Physiol Neurobiol. 169, 133-140 (2009).</li><li>Goshgarian, H. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+crossed+phrenic+phenomenon+and+recovery+of+function+following+spinal+cord+injury.">The crossed phrenic phenomenon and recovery of function following spinal cord injury.</a> Respir Physiol Neurobiol. 169, 85-93 (2009).</li><li>Nantwi, K. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+respiratory+activity+after+C2+hemisection+(C2HS):+involvement+of+adenosinergic+mechanisms.">Recovery of respiratory activity after C2 hemisection (C2HS): involvement of adenosinergic mechanisms.</a> Respir Physiol Neurobiol. 169, 102-114 (2009).</li><li>Sandhu, M. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Respiratory+recovery+following+high+cervical+hemisection.">Respiratory recovery following high cervical hemisection.</a> Respir Physiol Neurobiol. 169, 94-101 (2009).</li><li>Lane, M. A., Lee, K. Z., Fuller, D. D., Reier, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spinal+circuitry+and+respiratory+recovery+following+spinal+cord+injury.">Spinal circuitry and respiratory recovery following spinal cord injury.</a> Respir Physiol Neurobiol. 169, 123-132 (2009).</li><li>Seeds, N. W., Akison, L., Minor, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+plasminogen+activator+in+spinal+cord+remodeling+after+spinal+cord+injury.">Role of plasminogen activator in spinal cord remodeling after spinal cord injury.</a> Respir Physiol Neurobiol. 169, 141-149 (2009).</li><li>Alilain, W. J., Horn, K. P., Hu, H., Dick, T. E., Silver, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+regeneration+of+respiratory+pathways+after+spinal+cord+injury.">Functional regeneration of respiratory pathways after spinal cord injury.</a> Nature. 475, 196-200 (2011).</li><li>Vinit, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cervical+spinal+cord+injuries+and+respiratory+insufficiency:+a+revolutionary+treatment.">Cervical spinal cord injuries and respiratory insufficiency: a revolutionary treatment.</a> Med Sci (Paris. 28, 33-36 (2012).</li><li>Kastner, A., Gauthier, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Are+rodents+an+appropriate+pre-clinical+model+for+treating+spinal+cord+injury?+Examples+from+the+respiratory+system).">Are rodents an appropriate pre-clinical model for treating spinal cord injury? Examples from the respiratory system).</a> Exp Neurol. 213, 249-256 (2008).</li><li>Vinit, S., Lovett-Barr, M. R., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intermittent+hypoxia+induces+functional+recovery+following+cervical+spinal+injury.">Intermittent hypoxia induces functional recovery following cervical spinal injury.</a> Physiol Neurobiol. 169, 210-217 (2009).</li><li>Porter, W. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Path+of+the+Respiratory+Impulse+from+the+Bulb+to+the+Phrenic+Nuclei.">The Path of the Respiratory Impulse from the Bulb to the Phrenic Nuclei.</a> J Physiol. 17, 455-485 .</li><li>Nicaise, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Phrenic+motor+neuron+degeneration+compromises+phrenic+axonal+circuitry+and+diaphragm+activity+in+a+unilateral+cervical+contusion+model+of+spinal+cord+injury.">Phrenic motor neuron degeneration compromises phrenic axonal circuitry and diaphragm activity in a unilateral cervical contusion model of spinal cord injury.</a> Exp Neurol. 235, 539-552 (2012).</li><li>Goshgarian, H. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+crossed+phrenic+phenomenon:+a+model+for+plasticity+in+the+respiratory+pathways+following+spinal+cord+injury.">The crossed phrenic phenomenon: a model for plasticity in the respiratory pathways following spinal cord injury.</a> J Appl Physiol. 94, 795-810 (2003).</li><li>Vinit, S., Gauthier, P., Stamegna, J. C., Kastner, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=High+cervical+lateral+spinal+cord+injury+results+in+long-term+ipsilateral+hemidiaphragm+paralysis.">High cervical lateral spinal cord injury results in long-term ipsilateral hemidiaphragm paralysis.</a> J Neurotrauma. 23, 1137-1146 (2006).</li><li>Fuller, D. D., Johnson, S. M., Johnson, R. A., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+cervical+spinal+sensory+denervation+reveals+ineffective+spinal+pathways+to+phrenic+motoneurons+in+the+rat.">Chronic cervical spinal sensory denervation reveals ineffective spinal pathways to phrenic motoneurons in the rat.</a> Neurosci Lett. 323, 25-28 (2002).</li><li>Dougherty, B. J., Lee, K. Z., Lane, M. A., Reier, P. J., Fuller, D. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contribution+of+the+spontaneous+crossed-phrenic+phenomenon+to+inspiratory+tidal+volume+in+spontaneously+breathing+rats.">Contribution of the spontaneous crossed-phrenic phenomenon to inspiratory tidal volume in spontaneously breathing rats.</a> J Appl Physiol. 112, 96-105 (2012).</li><li>Jou, I. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Simplified+rat+intubation+using+a+new+oropharyngeal+intubation+wedge.">Simplified rat intubation using a new oropharyngeal intubation wedge.</a> J Appl Physiol. 89, 1766-1770 (2000).</li><li>Fuller, D. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Graded+unilateral+cervical+spinal+cord+injury+and+respiratory+motor+recovery.">Graded unilateral cervical spinal cord injury and respiratory motor recovery.</a> Respir Physiol Neurobiol. 165, 245-253 (2009).</li><li>Vinit, S., Windelborn, J. A., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lipopolysaccharide+attenuates+phrenic+long-term+facilitation+following+acute+intermittent+hypoxia.">Lipopolysaccharide attenuates phrenic long-term facilitation following acute intermittent hypoxia.</a> Respir Physiol Neurobiol. 176, 130-135 (2011).</li><li>Ahmad, F., Wang, M. Y., Levi, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hypothermia+for+Acute+Spinal+Cord+Injury-A+Review.">Hypothermia for Acute Spinal Cord Injury-A Review.</a> World Neurosurg. , (2013).</li><li>Lovett-Barr, M. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repetitive+intermittent+hypoxia+induces+respiratory+and+somatic+motor+recovery+after+chronic+cervical+spinal+injury.">Repetitive intermittent hypoxia induces respiratory and somatic motor recovery after chronic cervical spinal injury.</a> J Neurosci. 32, 3591-3600 (2012).</li><li>Minor, K. H., Akison, L. K., Goshgarian, H. G., Seeds, N. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spinal+cord+injury-induced+plasticity+in+the+mouse--the+crossed+phrenic+phenomenon.">Spinal cord injury-induced plasticity in the mouse--the crossed phrenic phenomenon.</a> Exp Neurol. 200, 486-495 (2006).</li><li>Baussart, B., Stamegna, J. C., Polentes, J., Tadie, M., Gauthier, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+new+model+of+upper+cervical+spinal+contusion+inducing+a+persistent+unilateral+diaphragmatic+deficit+in+the+adult+rat.">A new model of upper cervical spinal contusion inducing a persistent unilateral diaphragmatic deficit in the adult rat.</a> Neurobiol Dis. 22, 562-574 (2006).</li><li>Golder, F. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Breathing+patterns+after+mid-cervical+spinal+contusion+in+rats.">Breathing patterns after mid-cervical spinal contusion in rats.</a> Exp Neurol. 231, 97-103 (2011).</li><li>Lane, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Respiratory+function+following+bilateral+mid-cervical+contusion+injury+in+the+adult+rat.">Respiratory function following bilateral mid-cervical contusion injury in the adult rat.</a> Exp Neurol. 235, 197-210 (2012).</li><li>Vinit, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Axotomized+bulbospinal+neurons+express+c-Jun+after+cervical+spinal+cord+injury.">Axotomized bulbospinal neurons express c-Jun after cervical spinal cord injury.</a> Neuroreport. 16, 1535-1539 (2005).</li><li>Guenther, C. H., Windelborn, J. A., Tubon, T. C., Yin, J. C., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+atypical+PKC+expression+and+activity+in+the+phrenic+motor+nucleus+following+cervical+spinal+injury.">Increased atypical PKC expression and activity in the phrenic motor nucleus following cervical spinal injury.</a> Exp Neurol. 234, 513-520 (2012).</li><li>Mantilla, C. B., Gransee, H. M., Zhan, W. Z., Sieck, G. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Motoneuron+BDNF/TrkB+signaling+enhances+functional+recovery+after+cervical+spinal+cord+injury.">Motoneuron BDNF/TrkB signaling enhances functional recovery after cervical spinal cord injury.</a> Exp Neurol. 247, 101-109 (2013).</li><li>Vinit, S., Darlot, F., Aoulaiche, H., Boulenguez, P., Kastner, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Distinct+expression+of+c-Jun+and+HSP27+in+axotomized+and+spared+bulbospinal+neurons+after+cervical+spinal+cord+injury.">Distinct expression of c-Jun and HSP27 in axotomized and spared bulbospinal neurons after cervical spinal cord injury.</a> J Mol Neurosci. 45, 119-133 (2011).</li><li>Windelborn, J. A., Mitchell, G. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glial+activation+in+the+spinal+ventral+horn+caudal+to+cervical+injury.">Glial activation in the spinal ventral horn caudal to cervical injury.</a> Respir Physiol Neurobiol. 180, 61-68 (2012).</li><li>Vinit, S., Stamegna, J. C., Boulenguez, P., Gauthier, P., Kastner, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Restorative+respiratory+pathways+after+partial+cervical+spinal+cord+injury:+role+of+ipsilateral+phrenic+afferents.">Restorative respiratory pathways after partial cervical spinal cord injury: role of ipsilateral phrenic afferents.</a> Eur J Neurosci. 25, 3551-3560 (2007).</li><li>Dougherty, B. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+inspiratory+intercostal+muscle+activity+following+high+cervical+hemisection.">Recovery of inspiratory intercostal muscle activity following high cervical hemisection.</a> Respir Physiol Neurobiol. 183, 186-192 (2012).</li></ol>

Technical Difficulties of Making the C2 Injury Model
The C2 injury murine model is an interesting tool to study respiratory post-lesional neuroplasticity. However, the steps needed to produce a reproducible and reliable model are numerous and each one could impact on the outcome of the study. For example, during the intubation process, extreme care is to be taken since the orotracheal tube can produce an inflammation of the trachea, which can lead to diverse complications such...

Spinal cord trauma is a common injury observed in the human population with dramatic incidences, such as permanent paralysis. However, the severity of the injury depends on the level and the extent of the initial trauma. Respiratory failure is the leading cause of mortality following upper cervical spinal cord injury (SCI)1. Currently, the only therapeutic treatment is to place the patient under ventilatory assistance. Since few patients can be weaned off the ventilatory assistance2, due to spontaneous recovery which occurs with post-lesional delay, the need to develop new innovative non-invasive therapeutics is urgent3. Having a good standardized pre-clinical model to investigate the effect of a cervical SCI on respiratory insufficiency and therefore, to study the application of putative therapeutic strategies, is essential.
In this technical article, we describe a specific pre-clinical murine model of respiratory impairment induced by a partial cervical SCI at the C2 level. This model is currently used by several laboratories around the world (for reviews: 4-13). However, slight differences in the surgical procedure can be observed among the different investigators to generate this particular cervical injury murine model. The effect of a C2 SCI on the respiratory output was first described in 1895 by Porter14. A cervical hemisection induces a deafferentation of the phrenic motoneurons from their central drive (located in the rVRG in the brainstem, Figure 1A) on the ipsilateral side of injury, leading to a silent phrenic nerve activity and the subsequent diaphragm paralysis. The contralateral side remains intact and allows the animal to survive. Unlike different SCI located in a lower spinal segment (for example a contusive injury at C4 level15), the integrity of the phrenic motoneuron nucleus on both side is preserved. After a cervical C2 injury, some spontaneous activity can be observed on the ipsilateral side (phrenic and diaphragm) due to an activation of contralateral silent synaptic pathways which crossed the spinal midline at the segmental level C3-C6 (Crossed phrenic pathways, CPP, Figure 1B). The activation of the CPP, which is, by definition, a C2 hemisection combined with a contralateral phrenicotomy which induce an ipsilateral partial phrenic nerve recovery, can occur from hours to weeks post-injury16-18. The real beneficial effect of this CPP pathway on the respiratory recovery is limited19 and further investigation and treatment should be developed to improve the magnitude of spontaneous restoration3.
This protocol provides a powerful type of pre-clinical murine model to study respiratory post-lesional plasticity at various levels (respiratory physiology from pre and phrenic motoneurons, interneurons, molecular and cellular, locomotion of the front limb for example) as well as a model to test invasive and non-invasive therapeutic strategies aimed to improve the respiratory and locomotor recovery following C2 partial cervical spinal cord injury.

<table border="0" cellpadding="0" cellspacing="0" width="573">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<td colspan="4" height="21" style="height:21px;width:572px;">Animal</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Male Sprague Dawley Rat</td>
			<td>Janvier</td>
			<td></td>
			<td>225-250g</td>
		</tr>
		<tr height="21">
			<td colspan="4" height="21" style="height:21px;">Surgical Instruments</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Student Dumont #5 forceps</td>
			<td>Fine Science Tool</td>
			<td>91150-20</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Student Standard Pattern Forceps</td>
			<td>Fine Science Tool</td>
			<td>91100-12</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Mayo-Stille Scissors</td>
			<td>Fine Science Tool</td>
			<td>14013-15</td>
			<td>Curved</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Student Vannas Spring Scissors</td>
			<td>Fine Science Tool</td>
			<td>91500-09</td>
			<td>Straight</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Spring Scissors - 8 mm Blades</td>
			<td>Fine Science Tool</td>
			<td>15025-10</td>
			<td>Straight Blunt/Blunt</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Friedman Pearson Rongeur</td>
			<td>Fine Science Tool</td>
			<td>16121-14</td>
			<td>Curved</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Dissecting Knife - Fine Tip</td>
			<td>Fine Science Tool</td>
			<td>10055-12</td>
			<td>Straight</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Olsen-Hegar Needle Holder</td>
			<td>Fine Science Tool</td>
			<td>12002-14</td>
			<td>Serrated</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Weitlaner-Locktite Retractor</td>
			<td>Fine Science Tool</td>
			<td>17012-11</td>
			<td>2x3 Blunt</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Absorbable surgical sutures</td>
			<td>Centravet</td>
			<td>BYO001</td>
			<td></td>
		</tr>
		<tr height="21">
			<td colspan="4" height="21" style="height:21px;">Equipment</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Hot Bead Steriliser</td>
			<td>Fine Science Tool</td>
			<td>18000-45</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Catheter&#160;</td>
			<td>Centravet</td>
			<td>CAT188</td>
			<td>16 gauge</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Laryngoscope</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Guide wire</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Laryngeal mirror</td>
			<td>Centravet</td>
			<td>MIR011</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Lactated Ringers</td>
			<td>Centravet</td>
			<td>RIN020</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Syringe</td>
			<td>Centravet</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Needle</td>
			<td>Centravet</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="25">
			<td height="25" style="height:25px;">O2</td>
			<td>Air Liquid</td>
			<td>I1001M20R2A001</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">683 RodentT Ventilator 115/230V</td>
			<td>Havard Apparatus</td>
			<td>55-0000</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stand-Alone Vaporizer</td>
			<td>WPI</td>
			<td>EZ-155</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Thin line heated bed</td>
			<td>WPI</td>
			<td>EZ-211</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Air canister</td>
			<td>WPI</td>
			<td>EZ-258</td>
			<td></td>
		</tr>
		<tr height="21">
			<td colspan="4" height="21" style="height:21px;">Drugs</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Carprofen</td>
			<td>Centravet</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Rimadyl</td>
			<td>Centravet</td>
			<td>RIM011</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Buprenorphine</td>
			<td>Centravet</td>
			<td>BUP001</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Baytril</td>
			<td>Centravet</td>
			<td>BAY001</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Dexmedetomidine</td>
			<td>Centravet</td>
			<td>DEX010</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Atipamezole</td>
			<td>Centravet</td>
			<td>ANT201</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Betadine Solution</td>
			<td>Centravet</td>
			<td>VET002</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Isoflurane</td>
			<td>Centravet</td>
			<td>VET066</td>
			<td></td>
		</tr>
	</tbody>
</table>

a murine model of cervical spinal cord injury to study post-lesional respiratory neuroplasticity

A cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed to improve/ameliorate the respiratory failure following high cervical spinal cord injury (SCI). Here we propose a murine pre-clinical model of high SCI at the cervical 2 (C2) metameric level to study diverse post-lesional respiratory neuroplasticity. The technique consists of a surgical partial injury at the C2 level, which will induce a hemiparalysis of the diaphragm due to a deafferentation of the phrenic motoneurons from the respiratory centers located in the brainstem. The contralateral side of the injury remains intact and allows the animal recovery. Unlike other SCIs which affect the locomotor function (at the thoracic and lumbar level), the respiratory function does not require animal motivation and the quantification of the deficit/recovery can be easily performed (diaphragm and phrenic nerve recordings, whole body ventilation). This pre-clinical C2 SCI model is a powerful, useful, and reliable pre-clinical model to study various respiratory and non-respiratory neuroplasticity events at different levels (molecular to physiology) and to test diverse putative therapeutic strategies which might improve the respiration in SCI patients.

Extent of Injury
The success and the reproducibility of this particular experimental model are dependent on the experience of each manipulator/surgeon. The subsequent amount of respiratory recovery (phrenic nerve activity and diaphragm activity) following a C2 injury is correlated with the remaining ventrolateral spared white matter21. Since the injury is &#8220;handmade&#8221; and requires some practice from the surgeon, the extent of each injury has to be checked ...

Watch this Scientific Journal Video about A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity Video at JoVE.com

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity Video (Video) | JoVE

Respiratory failure is the leading cause of death following a cervical spinal cord injury. Having a reproducible, quantifiable, and reliable pre-clinical animal model of respiratory failure induced by a partial cervical injury will help to understand the subsequent respiratory and non-respiratory neuroplasticity and allow testing putative repair strategies.

A Murine Model of Cervical Spinal Cord Injury to Study Post-lesional Respiratory Neuroplasticity

A cervical spinal cord injury induces permanent paralysis, and often leads to respiratory distress. To date, no efficient therapeutics have been developed ...

Research

JoVE Journal

Medicine

Intraspinal Cell Transplantation for Targeting Cervical Ventral Horn in Amyotrophic Lateral Sclerosis and Traumatic Spinal Cord Injury

Intraspinal Cell Transplantation for Targeting Cervical Ventral Horn in Amyotrophic Lateral Sclerosis and Traumatic Spinal Cord Injury Video (Video) | JoVE

Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) ...

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats

Acute and Chronic Tactile Sensory Testing after Spinal Cord Injury in Rats Video (Video) | JoVE

Spinal cord injury (SCI) impairs sensory systems causing allodynia1-8. To identify cellular and molecular causes of allodynia, sensitive and valid sensory ...

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor Video (Video) | JoVE

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of ...

Controlled Cervical Laceration Injury in Mice

Controlled Cervical Laceration Injury in Mice Video (Video) | JoVE

Use of genetically modified mice enhances our  understanding of molecular mechanisms underlying several neurological disorders  such as a spinal cord ...

A Contusion Model of Severe Spinal Cord Injury in Rats

A Contusion Model of Severe Spinal Cord Injury in Rats Video (Video) | JoVE

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment (RMCA) in Individuals with Chronic Spinal Cord Injury

Evaluation of Respiratory Muscle Activation Using Respiratory Motor Control Assessment RMCA in Individuals with Chronic Spinal Cord Injury Video (Video) | JoVE

During breathing, activation of respiratory muscles is coordinated by integrated input from the brain, brainstem, and spinal cord. When this coordination ...

Controlled Cortical Impact Model for Traumatic Brain Injury

Controlled Cortical Impact Model for Traumatic Brain Injury Video (Video) | JoVE

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts

A Radio-telemetric System to Monitor Cardiovascular Function in Rats with Spinal Cord Transection and Embryonic Neural Stem Cell Grafts Video (Video) | JoVE

High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter ...

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury Video (Video) | JoVE

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. ...

Calibrated Forceps Model of Spinal Cord Compression Injury

Calibrated Forceps Model of Spinal Cord Compression Injury Video (Video) | JoVE

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The ...