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

Keomani, Emilie; Deramaudt, Thérèse B.; Petitjean, Michel; Bonay, Marcel; Lofaso, Frédéric; Vinit, Stéphane

doi:10.3791/51235

Cited by 14 publications

(13 citation statements)

References 35 publications

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“…However, all injured animals exhibited some spontaneous recovery acutely post-injury in this unanesthetized, decerebrate preparation. Histological analysis of the lesion epicenter revealed fairly consistent sparing of dorsomedial, intermediate gray and ventromedial white matter (Figure 1C), as described previously for incomplete C2Hx (Fuller et al, 2009; Keomani et al, 2014; Vinit et al, 2007). …”

Section: Resultssupporting

confidence: 80%

Supraspinal respiratory plasticity following acute cervical spinal cord injury

Bezdudnaya

Marchenko

Zholudeva

et al. 2017

Experimental Neurology

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Impaired breathing is a devastating result of high cervical spinal cord injuries (SCI) due to partial or full denervation of phrenic motoneurons, which innervate the diaphragm – a primary muscle of respiration. Consequently, people with cervical level injuries often become dependent on assisted ventilation and are susceptible to secondary complications. However, there is mounting evidence for limited spontaneous recovery of respiratory function following injury, demonstrating the neuroplastic potential of respiratory networks. Although many studies have shown such plasticity at the level of the spinal cord, much less is known about the changes occurring at supraspinal levels post-SCI. The goal of this study was to determine functional reorganization of respiratory neurons in the medulla acutely (>4 hours) following high cervical SCI. Experiments were conducted in decerebrate, unanesthetized, vagus intact and artificially ventilated rats. In this preparation, spontaneous recovery of ipsilateral phrenic nerve activity was observed within 4 to 6 hours following an incomplete, C2 hemisection (C2Hx). Electrophysiological mapping of the ventrolateral medulla showed a reorganization of inspiratory and expiratory sites ipsilateral to injury. These changes included i) decreased respiratory activity within the caudal ventral respiratory group (cVRG; location of bulbospinal expiratory neurons); ii) increased proportion of expiratory phase activity within the rostral ventral respiratory group (rVRG; location of inspiratory bulbo-spinal neurons); iii) increased respiratory activity within ventral reticular nuclei, including lateral reticular (LRN) and paragigantocellular (LPGi) nuclei. We conclude that disruption of descending and ascending connections between the medulla and spinal cord leads to immediate functional reorganization within the supraspinal respiratory network, including neurons within the ventral respiratory column and adjacent reticular nuclei.

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Section: Resultssupporting

confidence: 80%

Supraspinal respiratory plasticity following acute cervical spinal cord injury

Bezdudnaya

Marchenko

Zholudeva

et al. 2017

Experimental Neurology

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“…This type of injury compromises direct (monosynaptic) projections from the ventral respiratory column in the medulla to ipsilateral phrenic motoneurons (Ellenberger and Feldman, 1988; Ellenberger et al, 1990; Keomani et al, 2014; Lane et al, 2009b; Lane et al, 2008; Vinit and Kastner, 2009a), and results in an ipsilateral hemidiaphragm paralysis (Figure 1). Despite the extent of injury, acute partial recovery of phrenic and hemidiaphragm activity after C2Hx can be accomplished by a subsequent contralateral phrenicotomy (Goshgarian, 2003a; Porter, 1895) or by inducing a respiratory stress such as asphyxia, hypoxia or hypercapnia (Golder and Mitchell, 2005; Lewis and Brookhart, 1951).…”

Section: Plasticity After Cervical Scimentioning

confidence: 99%

Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury

Hormigo

Zholudeva

Spruance

et al. 2017

Experimental Neurology

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Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals. One strategy with demonstrated therapeutic potential is the use of treatments that increase neural and muscular activity (e.g. locomotor training, neural and muscular stimulation) and promote plasticity. With a focus on respiratory function post-SCI, this review will discuss advances in the use of neural interfacing strategies and activity-based treatments, and highlights some recent results from our own research.

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“…For both Studies, spinal hemisections at the second cervical segment (C2Hs) were performed in accordance with previous publications (Dougherty et al, 2012; Keomani et al, 2014; Navarrete-Opazo et al, 2015; Sandhu et al, 2009). Rats were pre-medicated with subcutaneous buprenorphine (0.03 mg/kg), carprofen (Rimadyl, 5 mg/kg) and enrofloxacin (Baytril, 4 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

Daily acute intermittent hypoxia improves breathing function with acute and chronic spinal injury via distinct mechanisms

Dougherty

Terada

Springborn

et al. 2018

Respiratory Physiology & Neurobiology

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Daily acute intermittent hypoxia (dAIH) elicits respiratory plasticity, enhancing respiratory motor output and restoring breathing capacity after incomplete cervical spinal injuries (cSCI). We hypothesized that dAIH-induced functional recovery of breathing capacity would occur after both acute (2 weeks) and chronic (8 weeks) cSCI, but through distinct cellular mechanisms. Specifically, we hypothesized that dAIH-induced breathing recovery would occur through serotonin-independent mechanisms 2wks post C2 cervical hemisection (C2Hs), versus serotonin-dependent mechanisms 8wks post C2Hs. In two independent studies, dAIH or sham (normoxia) was initiated 1 week (Study 1) or 7 weeks (Study 2) post-C2Hs to test our hypothesis. Rats were pre-treated with intra-peritoneal vehicle or methysergide, a broad-spectrum serotonin receptor antagonist, to determine the role of serotonin signaling in dAIH-induced functional recovery. Our data support the hypothesis that dAIH-induced recovery of breathing capacity transitions from a serotonin-independent mechanism with acute C2Hs to a serotonin-dependent mechanism with chronic C2Hs. An understanding of shifting mechanisms giving rise to dAIH-induced respiratory motor plasticity is vital for clinical translation of dAIH as a therapeutic modality.

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

Cited by 14 publications

References 35 publications

Supraspinal respiratory plasticity following acute cervical spinal cord injury

Supraspinal respiratory plasticity following acute cervical spinal cord injury

Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury

Daily acute intermittent hypoxia improves breathing function with acute and chronic spinal injury via distinct mechanisms

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