Neuropathology of distinct diaphragm areas following mid-cervical spinal cord contusion in the rat

BACKGROUND: The diaphragm is innervated by phrenic motoneurons distributed from the third to fifth cervical spinal cord. The rostral to caudal phrenic motoneuron pool segmentally innervates the ventral, medial, and dorsal diaphragm. PURPOSE: The present study was designed to investigate the physiological and transcriptomic mechanism of neuropathology of distinct diaphragm areas following mid-cervical spinal cord injury. STUDY DESIGN: In vivo animal study. METHODS: Electromyograms and transcriptome of the ventral, medial, and dorsal diaphragm were examined in rats that received cervical laminectomy or mid-cervical spinal cord contusion in the acute (ie, 1-3 days) or subchronic (ie, similar to 14 days) injury stages. RESULTS: Mid-cervical spinal cord contusion significantly attenuated the inspiratory bursting amplitude of the dorsal diaphragm but not the ventral or medial diaphragm. Moreover, the dis-charge onset of the dorsal diaphragm was significantly delayed compared with that of the ventral and medial diaphragm in contused rats. Transcriptomic analysis revealed a robust change in gene expression in the ventral diaphragm compared with that in the dorsal diaphragm. Specifically, enrichment analysis of differentially expressed genes demonstrated that the cell cycle and immune response were significantly upregulated, whereas several metabolic pathways were downregulated, in the ventral diaphragm of acutely contused rats. However, no significant Kyoto Encyclopedia of Genes and Genomes pathway was altered in the dorsal diaphragm. CONCLUSIONS: These results suggest that mid-cervical spinal cord injury has different impacts on the physiological and transcriptomic responses of distinct diaphragm areas. CLINICAL SIGNIFICANCE: Future therapeutic strategies can consider applying different therapies to distinct diaphragm areas following cervical spinal cord injury. Additionally, confirmation of activities across different diaphragm areas may provide a critical reference for the placement of diaphragmatic pacing electrodes. (C) 2022 Elsevier Inc. All rights reserved.