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While COPD primarily affects the lungs, emerging research shows the life-threatening role of associated systemic changes affecting other organs, including the brain. However, the complex interplay between COPD and the brain\u2019s microenvironment remains poorly understood. Here, we monitored alterations across several brain regions in mouse models subjected to chronic mild hypoxia (CMH) or tobacco-smoke exposure leading to pulmonary hypertension (S-PH) or also emphysema (S-Em). Brain microvasculature, microglia and hypoxia pathway states were analyzed by immunofluorescence and immunohistochemistry imaging of standard FFPE tissue sections. Quantitative evaluation revealed model-specific changes in microvascular density, with increased density in the CMH and S-Em and decreased density in the S-PH mice. 3D-imaging of cleared thick brain tissue sections by spinning-disc confocal microscopy corroborated these findings and, together with fibrinogen, MMP-9 and TIMP-1 immunoblot analyses, provided a comprehensive view of the distinct microenvironment states. Overall, our findings link lung dysfunction and associated changes in the brain microenvironment, which may be relevant to understanding the systemic comorbidities of chronic lung diseases, particularly altered brain conditions that may influence lung cancer metastasis.<\/jats:p>","DOI":"10.1038\/s41598-026-45975-3","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T18:15:25Z","timestamp":1776449725000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hypoxia or tobacco-smoke exposure induce region-specific microvascular remodeling in the brain"],"prefix":"10.1038","volume":"16","author":[{"given":"Nazli","family":"Salik Demirtas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edma","family":"Loku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Porschen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Sch\u00e4ffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Yu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Rummel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hadzic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Weissmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Acker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"N\u00e9meth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"45975_CR1","doi-asserted-by":"publisher","unstructured":"Barnes, P. 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Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am. J. Respir Crit. Care Med. 186, 155\u2013161. https:\/\/doi.org\/10.1164\/rccm.201201-0034OC (2012).","journal-title":"Am. J. Respir Crit. Care Med."},{"key":"45975_CR5","doi-asserted-by":"publisher","first-page":"1036387","DOI":"10.3389\/fneur.2023.1036387","volume":"14","author":"J Yu","year":"2023","unstructured":"Yu, J. et al. Association of smoking with the survival of patients with brain metastasis of lung cancer. Front. Neurol. 14, 1036387. https:\/\/doi.org\/10.3389\/fneur.2023.1036387 (2023).","journal-title":"Front. Neurol."},{"key":"45975_CR6","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1002\/cam4.1058","volume":"6","author":"RF Shenker","year":"2017","unstructured":"Shenker, R. F. et al. The Effects of smoking status and smoking history on patients with brain metastases from lung cancer. 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