Respiratory consequences of cervical spinal cord injury: insights from preclinical models

Respiratory dysfunction is one of the most common acute medical issues after cervical spinal cord injury (cSCI) and is considered a leading cause of reduced quality of life for long-term survivors. After cSCI, disruption of descending respiratory drive, impairment of respiratory muscle recruitment and altered airway protection combine to reduce ventilatory capacity and cough effectiveness, increasing the risk of atelectasis, pneumonia and ventilator dependence. Although modern intensive care and pulmonary rehabilitation have improved survival, respiratory complications remain a leading driver of hospitalisation, long-term disability and healthcare costs after cSCI. These clinical limitations highlight the need to explore novel therapeutic strategies and mechanistic targets that cannot be systematically tested in human studies and therefore require rigorous evaluation in preclinical models. This review synthesises clinical and preclinical evidence on how cervical injury compromises breathing, with emphasis on insights from experimental models that permit controlled manipulation of lesion level, severity and laterality to link specific injury characteristics to respiratory dysfunction. In particular, we outline the neural control of respiration (highlighting autonomous and volitional pathways linked to spinal respiratory motor pools), summarise the clinical trajectory of respiratory impairment and, finally, provide a comparison of widely used preclinical models, from their typical characteristic patterns of respiratory dysfunction to the lesion pathology that shapes recovery and interpretation of therapeutic studies.