Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat

Lee, Kun‐Ze

doi:10.1152/japplphysiol.00853.2018

Cited by 14 publications

(4 citation statements)

References 61 publications

(78 reference statements)

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“…Ventilatory behaviors (eg, respiratory frequency, tidal volume, and minute ventilation) of unanesthetized rats were measured using the whole-body plethysmography system (Buxco Whole Body Plethymography, Data Sciences International). 10,11,24,25 for 5 consecutive days beginning at 8 weeks (57 ± 1 days) postinjury. Rats were divided into 4 groups-DMSO + dAIH (n = 10); SB269970 + dAIH (n = 10); DMSO + Normoxia (n = 7); SB269970 + Normoxia (n = 6)-for the following experimental protocols.…”

Section: Whole-body Plethysmographymentioning

confidence: 99%

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5-HT7 Receptor Inhibition Transiently Improves Respiratory Function Following Daily Acute Intermittent Hypercapnic-Hypoxia in Rats With Chronic Midcervical Spinal Cord Contusion

Vinit

Chen

et al. 2020

Neurorehabil Neural Repair

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Background. Intermittent hypoxia can induce respiratory neuroplasticity to enhance respiratory motor outputs following hypoxic treatment. This type of respiratory neuroplasticity is primarily mediated by the activation of Gq-protein-coupled 5-HT2 receptors and constrained by Gs-protein-coupled 5-HT7 receptors. Objective. The present study hypothesized that the blockade of 5-HT7 receptors can potentiate the effect of intermittent hypercapnic-hypoxia on respiratory function after cervical spinal cord contusion injury. Methods. The ventilatory behaviors of unanesthetized rats with midcervical spinal cord contusions were measured before, during, and after daily acute intermittent hypercapnic-hypoxia (10 episodes of 5 minutes of hypoxia [10% O2, 4% CO2, 86% N2] with 5 minutes of normoxia intervals for 5 days) at 8 weeks postinjury. On a daily basis, 5 minutes before intermittent hypercapnic-hypoxia, rats received either a 5-HT7 receptor antagonist (SB269970, 4 mg/kg, intraperitoneal) or a vehicle (dimethyl sulfoxide). Results. Treatment with intermittent hypercapnic-hypoxia induced a similar increase in tidal volume between rats that received SB269970 and those that received dimethyl sulfoxide within 60 minutes post-hypoxia on the first day. However, after 2 to 3 days of daily acute intermittent hypercapnic-hypoxia, the baseline tidal volumes of rats treated with SB269970 increased significantly. Conclusions. These results suggest that inhibiting the 5-HT7 receptor can transiently improve daily intermittent hypercapnic-hypoxia–induced tidal volume increase in midcervical spinal contused animals. Therefore, combining pharmacological treatment with rehabilitative intermittent hypercapnic-hypoxia training may be an effective strategy for synergistically enhancing respiratory neuroplasticity to improve respiratory function following chronic cervical spinal cord injury.

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Section: Whole-body Plethysmographymentioning

confidence: 99%

“…The spinal cord area and lesion area at the lesion epicenter were manually outlined and quantified using Image J software, as previously described. 20,24…”

Section: Whole-body Plethysmographymentioning

confidence: 99%

5-HT7 Receptor Inhibition Transiently Improves Respiratory Function Following Daily Acute Intermittent Hypercapnic-Hypoxia in Rats With Chronic Midcervical Spinal Cord Contusion

Vinit

Chen

et al. 2020

Neurorehabil Neural Repair

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“…On the other hand, mid-and low-cervical SCIs partially spare phrenic motor neurons; nevertheless, there is still potential for respiratory impairment and reliance on ventilatory support depending on the extent of spared neural tissue following injury. Most SCIs are incomplete, sparing neurons and axonal pathways that can undergo compensatory plasticity, spontaneously improving function (36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Regardless, peak cough flow, maximal expiratory pressure, and maximal inspiratory pressure are diminished by cervical SCI especially at C5 and above (46).…”

Section: Spinal Cord Contusion Injurymentioning

confidence: 99%

Mechanisms of compensatory plasticity for respiratory motor neuron death

Seven

Mitchell

2019

Respiratory Physiology & Neurobiology

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Respiratory motor neuron death arises from multiple neurodegenerative and traumatic neuromuscular disorders. Despite motor neuron death, compensatory mechanisms minimize its functional impact by harnessing intrinsic mechanisms of compensatory respiratory plasticity. However, the capacity for compensation eventually reaches limits and pathology ensues. Initially, challenges to the system such as increased metabolic demand reveal sub-clinical pathology. With greater motor neuron loss, the eventual result is de-compensation, ventilatory failure, ventilator dependence and then death. In this brief review, we discuss recent advances in our understanding of mechanisms giving rise to compensatory respiratory plasticity in response to respiratory motor neuron death including: 1) increased central respiratory drive, 2) plasticity in synapses on spared phrenic motor neurons, 3) enhanced neuromuscular transmission and 4) shifts in respiratory muscle utilization from more affected to less affected motor pools. Some of these compensatory mechanisms may prolong breathing function, but hasten the demise of surviving motor neurons. Improved understanding of these mechanisms and their impact on survival of spared motor neurons will guide future efforts to develop therapeutic interventions that preserve respiratory function with neuromuscular injury/disease.

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“…Luckily, most SCIs in human patients are incomplete and therefore the neurons and descending pathways that are spared can undergo plasticity to compensate for function (Goshgarian, 2003;Goshgarian, 2009;Khurram et al, 2019;Lane et al, 2009;Lee, 2019;Lee and Hsu, 2017;Lee and Kuo, 2017;Mansel and Norman, 1990;Mantilla et al, 2013;Wen and Lee, 2018).…”

Section: Spinal Cord Injurymentioning

confidence: 99%

Evaluating the roles spinal plasticity and an accessory inspiratory muscle have in a rodent model of respiratory motor neuron death

Borkowski¹

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Death by ventilatory failure most frequently occurs in patients with neuromuscular diseases in which there is a loss of respiratory motor neurons. There are currently no significant treatments to prolong or correct for these respiratory deficits. Genetic rodent models of motor neuron loss develop many phenotypes (e.g., dysphagia, limb paralysis, etc.), so in order to study how motor neuron death only impacts respiration and to develop therapeutic interventions, we have developed an inducible model of respiratory motor neuron death. Briefly, rats are intrapleurally injected with cholera toxin B conjugated to saporin (CTB-SAP), which selectively eliminates respiratory motor neurons. Surprisingly, this model displays considerable respiratory plasticity that functions over time to preserve eupneic ventilation. Thus, the fundamental goal of this dissertation is to determine potential strategies that preserve eupneic ventilation following respiratory motor neuron loss. Our data suggest that respiratory plasticity requires different G-protein-coupled receptors and downstream signaling and that the exhibited plasticity is differentially affected by COX1/2-induced inflammation over the course of CTB-SAP induced neuropathology, which may collectively represent one way eupnea is maintained. Additional pilot data indicate diaphragmatic amplitude is decreased in CTB-SAP treated rats, which suggests that extradiaphragmatic muscles (e.g., accessory inspiratory muscles such as the pectoralis minor muscles that can be utilized in disease/injury) are also utilized to maintain eupneic ventilation. Our data suggest that pectoralis minor activity is increased in CTB-SAP rats vs. controls and is further increased in 28d vs. 7d CTBSAP rats. The overall hypotheses of this dissertation are that following CTB-SAP treatment: 1) respiratory plasticity requires differential activation of G-protein-coupled receptor pathways; 2) respiratory plasticity is differentially impacted by COX1/2-induced inflammation; and 3) pectoralis minor muscle amplitude is increased to maintain eupnea. This project will advance our understanding of potential targets (i.e., receptors, inflammatory markers, or muscles) that could be harnessed or stimulated to further preserve and/or improve ventilatory function and quality of life in patients with neuromuscular diseases that are suffering from respiratory motor neuron loss.

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Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat

Cited by 14 publications

References 61 publications

5-HT7 Receptor Inhibition Transiently Improves Respiratory Function Following Daily Acute Intermittent Hypercapnic-Hypoxia in Rats With Chronic Midcervical Spinal Cord Contusion

5-HT7 Receptor Inhibition Transiently Improves Respiratory Function Following Daily Acute Intermittent Hypercapnic-Hypoxia in Rats With Chronic Midcervical Spinal Cord Contusion

Mechanisms of compensatory plasticity for respiratory motor neuron death

Evaluating the roles spinal plasticity and an accessory inspiratory muscle have in a rodent model of respiratory motor neuron death

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