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The association of neural and molecular mechanisms between the infarcted brain area and the development of pneumonia and pulmonary dysfunction are not understood.<\/jats:p>\n                  <jats:p>We used whole-body plethysmography, the respiratory patterns test and arterial blood gas analysis to examine pulmonary function. In addition, Holter monitoring, electrophysiological recordings, chemogenetic manipulation, fibre photometry, ELISA, immunofluorescence, western blotting, reverse transcription-qPCR, haematoxylin and eosin staining, TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling) staining and viral-mediated manipulations were used to address our questions.<\/jats:p>\n                  <jats:p>Here, we observed significant pneumonia (immune cell infiltration and increased inflammatory cytokines) and pulmonary dysfunction in middle cerebral artery occlusion rats. A decrease in parasympathetic nerve function and activity was observed in clinical patients and rodent models with acute ischaemic stroke. Mechanistically, ischaemic stroke leads to the apoptosis of glutamatergic neurons in the paraventricular nucleus of the hypothalamus (PVNCaMKII) that innervate acetylcholine neurons in the dorsal motor nucleus of the vagus (DMVACh) and subsequently decreases the activity of DMVACh neurons. The reduced DMVACh neuron activity, via the \u03b17 nicotinic acetylcholine receptor (\u03b17nAChR), upregulates high mobility group box 1 (HMGB1) expression in the pulmonary parasympathetic ganglia neurons, which increases the expression of tumour necrosis factor-\u03b1 and interleukin-1\u03b2 in various immune cells via toll-like receptor 4 or the receptor for advanced glycation end products (RAGE). Meanwhile, the activation of circuit from DMVACh neurons to pulmonary parasympathetic ganglia neurons improved pneumonia and pulmonary dysfunction.<\/jats:p>\n                  <jats:p>These results dissect a novel neuroimmune framework that acute ischaemic stroke induces the apoptosis of DMVACh-innervating PVNCaMKII neurons, and subsequently promotes immune cell infiltration and increases in inflammatory cytokines via the \u03b17nAChR-HMGB1 pathway in the pulmonary ganglion neurons, which leads to pulmonary dysfunction. These results provide a novel insight into the pathogenesis of pneumonia and pulmonary dysfunction after acute ischaemic stroke.<\/jats:p>","DOI":"10.1093\/brain\/awaf254","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T07:38:53Z","timestamp":1751960333000},"page":"4562-4577","source":"Crossref","is-referenced-by-count":12,"title":["Brain regulation of pulmonary dysfunction induced by stroke"],"prefix":"10.1093","volume":"148","author":[{"given":"Meiying","family":"Chen","sequence":"first","affiliation":[{"name":"Guangdong Province Key Laboratory of Brain Function and Disease, Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University , 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510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Pain Medicine, Guangzhou First People\u2019s Hospital , Guangzhou, Guangdong 510000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Brain Function and Disease, Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yat-sen University , Guangzhou, Guangdong 510080 ,","place":["China"]},{"name":"Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Key Laboratory on Assisted Circulation , Guangzhou, Guangdong 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory for Cognitive and Developmental Disorders, Department of Anatomy, Medical College of Jinan University , Guangzhou, Guangdong 510630 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Key Laboratory on Assisted Circulation , Guangzhou, Guangdong 510080 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Guo","sequence":"additional","affiliation":[{"name":"Neuroscience Laboratory for Cognitive and Developmental Disorders, Department of Anatomy, Medical College of Jinan University , Guangzhou, Guangdong 510630 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Second Affiliated Hospital, Hengyang Medical School, 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