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by claude@2026-07, 2026-07-04
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The study investigated whether forelimb muscle afferent input from biceps brachii electrical stimulation can enhance respiratory output after cervical spinal cord injury, using rat models of acute C2 hemisected injury, complete C1 transection, and intact controls. The authors measured effects on phrenic nerve activity and respiratory patterns, and developed a computational model with bilateral brainstem and cervical spinal respiratory circuits to simulate how spinal and supraspinal components contribute under each injury condition. They found that biceps stimulation increased ipsilateral phrenic activity after C2 hemisection and drove bilateral phrenic output after complete C1 transection, but in the fully transected preparation the effect required pharmacological disinhibition, indicating latent spinal pathways. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Cervical spinal cord injuries (SCI) often lead to respiratory impairments, significantly increasing morbidity and mortality in affected individuals. Limb muscle/afferent stimulation has been suggested as a potential approach to enhance breathing when supraspinal control over spinal respiratory circuits is compromised due to cervical SCI. Using a combination of intact, C2 Hemisected (C2Hx), and complete C1 Transected (C1Tx) rat models, we systematically evaluated the influence of forelimb muscle afferent input on phrenic motor output and respiratory patterns. Computational modeling was employed to replicate our experimental data and generate predictions. The developed computational model incorporates bilaterally located spinal and supraspinal respiratory circuits, allowing us to simulate their specific contributions to phrenic motor output under different conditions. In this study, we hypothesize that, in addition to supraspinal control, spinal circuits integrate limb sensory input to modulate the activity of phrenic motor neurons through local excitatory and inhibitory interneurons. These intraspinal pathways, normally suppressed by inhibition, can be recruited during movement to adapt breathing to motor demands. Our experimental and computational modeling results following biceps stimulation after C2Hx and C1Tx support this hypothesis, demonstrating that activation of limb afferent pathways can enhance phrenic motor output even after partial or complete loss of supraspinal drive. In the fully transected preparation, this effect required pharmacological disinhibition, confirming the presence of latent spinal pathways. This study provides the first evidence for functionally relevant intraspinal interactions between limb muscles and respiratory circuits and identifies a potential spinal mechanism that could be leveraged to promote breathing recovery after cervical SCI. Key Points Biceps brachii electrical stimulation can increase breathing frequency and tidal volume in spontaneously breathing rats and variably induce transient increases or entrainment of phrenic nerve activity in intact rats under controlled ventilation. Biceps stimulation enhances ipsilateral phrenic activity in acute C2 hemisected (C2Hx) rats. Biceps stimulation drives bilateral phrenic output in C1 transected (C1Tx) rats under conditions of pharmacologically induced spinal disinhibition. A computational model incorporating bilateral brainstem and cervical spinal respiratory circuits is developed to simulate cervical spinal cord injuries (C2Hx and C1Tx) and to examine how biceps stimulation affects respiratory activity under different conditions. These findings demonstrate a critical role for spinal circuits in locomotor–respiratory interactions.
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Abstract
Cervical spinal cord injuries (SCI) often lead to respiratory impairments, significantly increasing morbidity and mortality in affected individuals. Limb muscle/afferent stimulation has been suggested as a potential approach to enhance breathing when supraspinal control over spinal respiratory circuits is compromised due to cervical SCI. Using a combination of intact, C2 Hemisected (C2Hx), and complete C1 Transected (C1Tx) rat models, we systematically evaluated the influence of forelimb muscle afferent input on phrenic motor output and respiratory patterns. Computational modeling was employed to replicate our experimental data and generate predictions. The developed computational model incorporates bilaterally located spinal and supraspinal respiratory circuits, allowing us to simulate their specific contributions to phrenic motor output under different conditions. In this study, we hypothesize that, in addition to supraspinal control, spinal circuits integrate limb sensory input to modulate the activity of phrenic motor neurons through local excitatory and inhibitory interneurons. These intraspinal pathways, normally suppressed by inhibition, can be recruited during movement to adapt breathing to motor demands. Our experimental and computational modeling results following biceps stimulation after C2Hx and C1Tx support this hypothesis, demonstrating that activation of limb afferent pathways can enhance phrenic motor output even after partial or complete loss of supraspinal drive. In the fully transected preparation, this effect required pharmacological disinhibition, confirming the presence of latent spinal pathways. This study provides the first evidence for functionally relevant intraspinal interactions between limb muscles and respiratory circuits and identifies a potential spinal mechanism that could be leveraged to promote breathing recovery after cervical SCI.
Biceps brachii electrical stimulation can increase breathing frequency and tidal volume in spontaneously breathing rats and variably induce transient increases or entrainment of phrenic nerve activity in intact rats under controlled ventilation.
Biceps stimulation enhances ipsilateral phrenic activity in acute C2 hemisected (C2Hx) rats.
Biceps stimulation drives bilateral phrenic output in C1 transected (C1Tx) rats under conditions of pharmacologically induced spinal disinhibition.
A computational model incorporating bilateral brainstem and cervical spinal respiratory circuits is developed to simulate cervical spinal cord injuries (C2Hx and C1Tx) and to examine how biceps stimulation affects respiratory activity under different conditions.
These findings demonstrate a critical role for spinal circuits in locomotor–respiratory interactions.
Competing Interest Statement
The authors have declared no competing interest.
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