Acute lung injury induces sustained neuroinflammation and dysfunction in the brainstem nucleus of the solitary tract of rats

Background Acute lung injury (ALI) causes profound pulmonary inflammation and is increasingly associated with neurological symptoms, suggesting that inflammatory signalling extends beyond the lungs to affect central nervous system circuits. However, the molecular and functional consequences of ALI in brainstem regions involved in respiratory control remain poorly defined. Here, we examined the impact of bleomycin-induced ALI on the nucleus of the solitary tract (NTS), the primary brainstem termination site of vagal sensory afferents from the lungs. Main body Using a rat model, a single intratracheal dose of bleomycin (7.5 mg/ kg) induced acute lung inflammation, persistent tissue pathology, and altered respiratory parameters lasting up to 28 days. Transcriptomic profiling of the NTS revealed widespread gene expression changes at both day 7 and day 28. Ranked gene set enrichment analysis showed that early transcriptional changes were characterised by positive enrichment of synaptic signalling and neurotransmission-related processes, together with negative enrichment of metabolic, lipid catabolic, and immune-associated pathways. By day 28, positively enriched pathways shifted towards mitochondrial and energy-generating processes, whereas negatively enriched pathways implicated synaptic organisation, neuronal guidance, and cell adhesion-related biology. Morphometric analysis of IBA1-positive microglia demonstrated significant changes in microglial morphology within the NTS at both time points, consistent with a reactive phenotype. Functionally, in vivo microinjections of capsaicin or L-glutamic acid into the NTS evoked significantly attenuated respiratory responses in bleomycin-treated rats compared with controls. Conclusion Bleomycin-induced ALI drives sustained neuroinflammatory and functional disruption in the NTS, a key brainstem hub for pulmonary vagal signalling. These findings provide new evidence for lung-to-brain communication in ALI and identify molecular pathways that may underlie impaired reflex control and broader neurological morbidity associated with respiratory disease.