Spinal circuitry and respiratory recovery following spinal cord injury

Lane, Megan; Lee, Kun‐Ze; Fuller, David D.; Reier, Paul J.

doi:10.1016/j.resp.2009.08.007

Cited by 134 publications

(142 citation statements)

References 87 publications

(117 reference statements)

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“…The subsequent inflammatory processes 33 and the cytoarchitectural changes (perineuronal net changes 10 ) have been investigated following a C2 SCI. The spinal structural changes (implication of substitutive pathways 34 and the involvement of spinal interneurons 8 ) or the ultrastructural changes at the diaphragm motor end plate 4 also actively participate in the spontaneous restoration of the respiratory activity following a C2 SCI. The most studied topic on the C2 SCI model is the physiological consequences of the initial injury on the entire respiratory system (Tidal volume, frequency in non-anesthetized animals 24 ) and its subsequent spontaneous recovery (on anesthetized preparations i.e.…”

Section: Uses For the C2 Injury Murine Modelmentioning

confidence: 99%

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

Keomani

Deramaudt

Petitjean

et al. 2014

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Citation: Keomani, E., Deramaudt, T.B., Petitjean, M., Bonay, M., Lofaso, F., Vinit, S. A Murine Model of Cervical Spinal Cord Injury to Study Postlesional Respiratory Neuroplasticity. J. Vis. Exp. (87), e51235, doi:10.3791/51235 (2014). AbstractA 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 preclinical 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. Video LinkThe video component of this article can be found at

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Section: Uses For the C2 Injury Murine Modelmentioning

confidence: 99%

“…This model is currently used by several laboratories around the world (for reviews: [4][5][6][7][8][9][10][11][12][13] ). However, slight differences in the surgical procedure can be observed among the different investigators to generate this particular cervical injury murine model.…”

Section: Introductionmentioning

confidence: 99%

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

Keomani

Deramaudt

Petitjean

et al. 2014

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“…These crossed phrenic pathways consist of latent bulbospinal pathways that cross below the site of SCI, 4 and possibly inputs from propriospinal interneurons located within the cervical spinal cord. 8,23 Multiple methods to restore function to the previously paralyzed hemidiaphragm have been examined in both males and females and, so far to date, enhancement of respiratory drive or synaptic input to phrenic motoneurons, or a decrease in inhibition, results in some restoration of phrenic activity below the site of SCI. 6,[25][26][27][28][29] Functionally, the activation of the crossed phrenic pathways appears to make a meaningful contribution to ventilation in anesthetized rats after SCI, 7,24,30 which may contribute even more during augmented breaths or sighs.…”

Section: Effect Of Sci On Muscles Controlling Ventilationmentioning

confidence: 99%

“…2 In all mammals, inspiration is accomplished primarily by the contraction of the diaphragm and aided by the activity of the intercostal muscles. The effect of SCI on diaphragm function has been well characterized [3][4][5][6][7][8] ; however, there are only a few examples of studies that have examined the effect of SCI on intercostal musculature. 9,10 It is well known that upper cervical SCI interrupts the neural signals arising from medullary respiratory neurons that project down the spinal cord to innervate ipsilateral phrenic motor neurons located in the cervical cord (C3-C6 in rats) resulting in ipsilateral hemidiaphragmatic paralysis.…”

Section: Introductionmentioning

confidence: 99%

Ipsilateral inspiratory intercostal muscle activity after C2 spinal cord hemisection in rats

Zimmer

Grant

Ayar

et al. 2014

The Journal of Spinal Cord Medicine

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Background: Upper cervical spinal cord hemisection causes paralysis of the ipsilateral hemidiaphragm; however, the effect of C2 hemisection on the function of the intercostal muscles is not clear. We hypothesized that C2 hemisection would eliminate inspiratory intercostal activity ipsilateral to the injury and that some activity would return in a time-dependent manner. Methods: Female Sprague Dawley rats were anesthetized with urethane and inspiratory intercostal electromyogram (EMG) activity was recorded in control rats, acutely injured C2 hemisected rats, and at 1 and 16 weeks post C2 hemisection. Results: Bilateral recordings of intercostal EMG activity showed that inspiratory activity was reduced immediately after injury and increased over time. EMG activity was observed first in rostral spaces followed by recovery occurring in caudal spaces. Theophylline increased respiratory drive and increased intercostal activity, inducing activity that was previously absent. Conclusion: These results suggest that there are crossed, initially latent, respiratory connections to neurons innervating the intercostal muscles similar to those innervating phrenic motor neurons.

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“…For example, compared to the intact spinal cord, increased numbers of cells can be delivered into a SCI site if a cavity has already formed 16 . However, the specific parameters need to be systematically optimized prior to undertaking a large study.…”

Section: Representative Resultsmentioning

confidence: 99%

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

Lepore

2011

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Respiratory compromise due to phrenic motor neuron loss is a debilitating consequence of a large proportion of human traumatic spinal cord injury (SCI) cases 1 and is the ultimate cause of death in patients with the motor neuron disorder, amyotrophic laterals sclerosis (ALS) 2 .ALS is a devastating neurological disorder that is characterized by relatively rapid degeneration of upper and lower motor neurons. Patients ultimately succumb to the disease on average 2-5 years following diagnosis because of respiratory paralysis due to loss of phrenic motor neuron innnervation of the diaphragm 3 . The vast majority of cases are sporadic, while 10% are of the familial form. Approximately twenty percent of familial cases are linked to various point mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene on chromosome 21 4 . Transgenic mice 4,5 and rats 6 carrying mutant human SOD1 genes (G93A, G37R, G86R, G85R) have been generated, and, despite the existence of other animal models of motor neuron loss, are currently the most highly used models of the disease.Spinal cord injury (SCI) is a heterogeneous set of conditions resulting from physical trauma to the spinal cord, with functional outcome varying according to the type, location and severity of the injury 7 . Nevertheless, approximately half of human SCI cases affect cervical regions, resulting in debilitating respiratory dysfunction due to phrenic motor neuron loss and injury to descending bulbospinal respiratory axons 1 . A number of animal models of SCI have been developed, with the most commonly used and clinically-relevant being the contusion 8 .Transplantation of various classes of neural precursor cells (NPCs) is a promising therapeutic strategy for treatment of traumatic CNS injuries and neurodegeneration, including ALS and SCI, because of the ability to replace lost or dysfunctional CNS cell types, provide neuroprotection, and deliver gene factors of interest 9 .Animal models of both ALS and SCI can model many clinically-relevant aspects of these diseases, including phrenic motor neuron loss and consequent respiratory compromise 10,11 . In order to evaluate the efficacy of NPC-based strategies on respiratory function in these animal models of ALS and SCI, cellular interventions must be specifically directed to regions containing therapeutically relevant targets such as phrenic motor neurons. We provide a detailed protocol for multi-segmental, intraspinal transplantation of NPCs into the cervical spinal cord ventral gray matter of neurodegenerative models such as SOD1 G93A mice and rats, as well as spinal cord injured rats and mice 11 . Video LinkThe video component of this article can be found at

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Spinal circuitry and respiratory recovery following spinal cord injury

Cited by 134 publications

References 87 publications

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

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

Ipsilateral inspiratory intercostal muscle activity after C2 spinal cord hemisection in rats

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

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