Rôle of the Vagi in the Crossed Phrenic Phenomenon

Chatfield, Paul O.; Mead, Sedgwick

doi:10.1152/ajplegacy.1948.154.3.417

Cited by 23 publications

(3 citation statements)

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“…Studies have shown that spinal cord hemisection rostral to the phrenic nucleus will permanently paralyze the ipsilateral hemidiaphragm (Aserinsky, 1961;Guth, 1976). However, if the phrenic nerve innervating the functioning side of the diaphragm is then cut (i.e., if the animal is subjected to respiratory stress), functional recovery is achieved in the hemidiaphragm paralyzed by spinal cord injury (Porter, 1895;Chatfield and Mead, 1948;Goshgarian and Guth, 1977). This hemidiaphragmatic recovery is thought to be mediated by a latent crossed phrenic pathway which descends into the spinal cord contralateral to the hemisection and crosses the midline of the spinal cord at the level of the phrenic nuclei (Moreno et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Synaptic plasticity of 5-hydroxytryptamine-immunoreactive terminals in the phrenic nucleus following spinal cord injury: A quantitative electron microscopic analysis

1997

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The present study was conducted to examine the plasticity of 5-hydroxytryptamine (5-HT)-immunoreactive terminals in the rat phrenic nucleus following an ipsilateral C2 spinal cord hemisection and 30-day survival period. A retrograde horseradish peroxidase (HRP) labeling technique was used to identify the phrenic motoneurons at the electron microscopic (EM) level. After employing a pre-embedding immunocytochemical technique, the ultrastructural characteristics of 5-HT-immunoreactive terminals were qualitatively and then quantitatively analyzed with a computerized morphometric system before and after injury in separate groups of rats. The results indicated that the majority of the 5-HT-labeled terminals formed axodendritic contacts, but some 5-HT-labeled terminals made axosomatic contacts. 5-HT terminals were associated with either asymmetrical or symmetrical synapses, and some displayed postsynaptic dense bodies. Approximately 2% of the 5-HT terminals had dense-core vesicles. Although the total number of labeled and unlabeled terminals in the phrenic nucleus was reduced after hemisection, the number of 5-HT terminals in the hemisected group was greater than that of the control group. Moreover, the total number and length of asymmetrical and symmetrical synaptic active zones per 5-HT terminal were significantly greater after injury. Finally, the total number of 5-HT terminals with multiple synapses was significantly greater in the hemisected group as compared to controls. It is possible that 5-HT synaptic plasticity may be part of the morphological substrate for the unmasking of the latent crossed phrenic pathway which mediates recovery of the ipsilateral hemidiaphragm paralyzed by C2 spinal cord hemisection.

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Section: Discussionmentioning

confidence: 99%

Synaptic plasticity of 5-hydroxytryptamine-immunoreactive terminals in the phrenic nucleus following spinal cord injury: A quantitative electron microscopic analysis

1997

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“…Further examination revealed that the amount of activity recorded from the previously paralyzed hemidiaphragm was proportional to the intensity of the respiratory drive (38). The presence of the crossed phrenic phenomenon has since been confirmed in dogs (37)(38)(39), cats (37)(38)(39)(40)(41), rabbits (37,(41)(42)(43), guinea pigs (44,45), rats (35,(46)(47)(48), mice (49), and even woodchucks (37).…”

Section: History Of the Crossed Phrenic Phenomenonmentioning

confidence: 96%

Effect of Spinal Cord Injury on the Respiratory System: Basic Research and Current Clinical Treatment Options

Zimmer

Nantwi

Goshgarian

2007

The Journal of Spinal Cord Medicine

154

126

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Summary: Spinal cord injury (SCI) often leads to an impairment of the respiratory system. The more rostral the level of injury, the more likely the injury will affect ventilation. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. This review highlights the progress that has been made in basic and clinical research, while noting the gaps in our knowledge. Basic research has focused on a hemisection injury model to examine methods aimed at improving respiratory function after SCI, but contusion injury models have also been used. Increasing synaptic plasticity, strengthening spared axonal pathways, and the disinhibition of phrenic motor neurons all result in the activation of a latent respiratory motor pathway that restores function to a previously paralyzed hemidiaphragm in animal models. Human clinical studies have revealed that respiratory function is negatively impacted by SCI. Respiratory muscle training regimens may improve inspiratory function after SCI, but more thorough and carefully designed studies are needed to adequately address this issue. Phrenic nerve and diaphragm pacing are options available to wean patients from standard mechanical ventilation. The techniques aimed at improving respiratory function in humans with SCI have both pros and cons, but having more options available to the clinician allows for more individualized treatment, resulting in better patient care. Despite significant progress in both basic and clinical research, there is still a significant gap in our understanding of the effect of SCI on the respiratory system.

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“…Crossed-phrenic pathways have been a target of extensive research as a substrate for recovery of breathing after cSCI. Although inactive in normal conditions, the CPP was originally observed when, after a C 2 hemisection (unilaterally interrupting bulbospinal inputs to the phrenic motor pool), ipsilesional hemidiaphragm paralysis was rapidly attenuated when the contralateral phrenic nerve was transected (72)(73)(74)(75)(76). Decades of research have been dedicated to elucidating the mechanisms underlying the CPP in an effort to restore ventilatory function after injury (for reviews, see Refs.…”

Section: Spontaneous Recovery After Cscimentioning

confidence: 99%

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury

Malone

Nosacka

Nash

et al. 2021

Journal of Neurophysiology

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Traumatic cervical spinal cord injury (cSCI) can lead to damage of bulbospinal pathways to the respiratory motor nuclei and consequent life-threatening respiratory insufficiency due to respiratory muscle paralysis/paresis. Reports of electrical epidural stimulation (EES) of the lumbosacral spinal cord to enable locomotor function after SCI are encouraging, with some evidence of facilitating neural plasticity. Here, we detail the development and success of EES in recovering locomotor function with consideration of stimulation parameters and safety measures to develop effective EES protocols. EES is just beginning to be applied in other motor, sensory, and autonomic systems; however, there has only been moderate success in preclinical studies aimed at improving breathing function after cSCI. Thus, we explore rationale for applying EES to the cervical spinal cord, targeting the phrenic motor nucleus for the restoration of breathing. We also suggest cellular/molecular mechanisms by which EES may induce respiratory plasticity including a brief examination of sex-related differences in these mechanisms. Finally, we suggest more attention be paid to the effects of specific electrical parameters that have been used in the development of EES protocols and how that can impact the safety and efficacy for those receiving this therapy. Ultimately, we aim to inform readers about the potential benefits of EES in the phrenic motor system and encourage future studies in this area.

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Rôle of the Vagi in the Crossed Phrenic Phenomenon

Cited by 23 publications

References 0 publications

Synaptic plasticity of 5-hydroxytryptamine-immunoreactive terminals in the phrenic nucleus following spinal cord injury: A quantitative electron microscopic analysis

Synaptic plasticity of 5-hydroxytryptamine-immunoreactive terminals in the phrenic nucleus following spinal cord injury: A quantitative electron microscopic analysis

Effect of Spinal Cord Injury on the Respiratory System: Basic Research and Current Clinical Treatment Options

Electrical epidural stimulation of the cervical spinal cord: implications for spinal respiratory neuroplasticity after spinal cord injury

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