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Although traditionally attributed to neuronal toxicity, emerging evidence suggests a key role of cerebrovascular dysfunction in its pathogenesis. We hypothesized that paclitaxel (PTX, Taxol) treatment induces long-term cerebrovascular dysfunction, including microvascular rarefaction, impaired neurovascular coupling (NVC), and altered cerebral blood flow (CBF), which contribute to CICI. Using a clinically relevant PTX treatment regimen in non-tumor-bearing mice, we evaluated the long-term effects of PTX on cerebrovascular health. Ultrasound localization microscopy (ULM) and functional ultrasound imaging (fUS) were employed to assess microvascular density, CBF, and NVC. PTX treatment resulted in a significant reduction in microvascular density in the cerebral cortex and hippocampus, key regions involved in cognitive function. PTX significantly reduced blood velocity in the middle cerebral artery. Moreover, PTX impaired NVC responses, as evidenced by a diminished CBF increase in response to whisker stimulation, indicative of impaired reactive hyperemia. In conclusion, these findings demonstrate that PTX induces long-lasting cerebrovascular dysfunction, including microvascular rarefaction, impaired NVC, and altered CBF dynamics, which likely contribute to CICI. This study underscores the critical role of cerebrovascular health in cognitive function and highlights the potential of targeting cerebrovascular pathways as a therapeutic approach for mitigating chemotherapy-induced cognitive deficits.<\/jats:p>","DOI":"10.1007\/s11357-025-01624-7","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T18:18:51Z","timestamp":1743099531000},"page":"4813-4825","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Functional ultrasound imaging reveals microvascular rarefaction, decreased cerebral blood flow, and impaired neurovascular coupling in a mouse model of paclitaxel-induced chemobrain"],"prefix":"10.1007","volume":"47","author":[{"given":"Siva Sai","family":"Chandragiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Nyul-Toth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Negri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Patai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Gulej","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boglarka","family":"Csik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santny","family":"Shanmugarama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana","family":"Vali Kordestan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Nagykaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mukli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5053-2828","authenticated-orcid":false,"given":"Anna","family":"Ungvari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriy","family":"Yabluchanskiy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Ungvari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Tarantini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Csiszar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,25]]},"reference":[{"key":"1624_CR1","doi-asserted-by":"publisher","first-page":"3348","DOI":"10.1002\/cncr.25098","volume":"116","author":"JS Wefel","year":"2010","unstructured":"Wefel JS, Saleeba AK, Buzdar AU, Meyers CA. 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Dr. Zoltan Ungvari serves as Editor-in-Chief for\n                      GeroScience\n                      and has personal relationships with individuals involved in the submission of this paper. The authors declare that these roles did not influence the study design, data interpretation, or manuscript preparation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The funding sources had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the American Heart Association.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Disclaimer"}}]}}