Selective vulnerability of the spinal cord in a rat model of asphyxia-induced cardiac arrest.

Spinal cord injury after cardiac arrest (CA) can cause devastating neurological deficits, including paraplegia. Although lumbar spinal cord injury is clinically important, regional comparisons remain limited. In this study, we examined region-associated vulnerability of the thoracic and lumbar spinal cord using a rat model of asphyxial CA (ACA). Adult male Sprague-Dawley rats underwent sham surgery or ACA, and thoracic and lumbar spinal cord tissues were collected 24 h after return of spontaneous circulation (ROSC) from ACA survivors with hindlimb paralysis. Histopathological analysis demonstrated significantly fewer surviving neurons in the lumbar compared with the thoracic spinal cord after ACA. The lumbar spinal cord also showed higher BAX/BCL2 ratios and cleaved caspase-3 expression, together with increased phosphorylation of NF-κB and mitogen-activated protein kinases, including p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Exploratory transcriptomic comparison between ACA-L and ACA-T identified 292 upregulated and 187 downregulated DEGs. Enrichment analyses indicated that upregulated DEGs were associated with extracellular matrix-receptor interaction, focal adhesion, integrin signaling, and PI3K-Akt signaling, whereas downregulated DEGs were associated with nervous system development and myelination. Collectively, these findings demonstrate region-dependent molecular and histopathological alterations at 24 h after ROSC, with a more pronounced injury-associated inflammatory and apoptosis-related profile in the lumbar spinal cord of paralyzed ACA survivors.