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In CCH, neuroinflammation by immune cells in the brain is a key pathological feature in the development of VaD. However, it is unclear whether the cells contributing to disease pathogenesis during CCH are resident microglia (MG) or infiltrating monocyte\u2010derived macrophages (M\u03a6s) owing to blood\u2013brain barrier disruption. Therefore, we applied bilateral common carotid artery stenosis (BCAS) to\n                    <jats:italic>Ccr2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>RFP<\/jats:italic>\n                      \/+\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Cx3cr1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>GFP<\/jats:italic>\n                      \/+\n                    <\/jats:sup>\n                    mice capable of distinguishing between MG and M\u03a6s and investigated MG activation and potential M\u03a6s infiltration during disease progression. We discovered that M\u03a6s did not infiltrate the brain up to four weeks after BCAS. In contrast, MG exhibited significant activation, predominantly to the pro\u2010inflammatory M1 phenotype. Additionally, methyldopa (MD), a compound we previously revealed to have lipid peroxidation (LPO) inhibitory property and which attenuated cognitive impairment in BCAS mice, reduced morphological changes and activation of MG during CCH. MD treatment decreased 4\u2010HNE\u2010modified proteins, indicating that LPO products contribute to neuroinflammation in CCH. These findings suggest that MG are activated prior to cognitive impairment by CCH and that LPO inhibitor can suppress MG activation, thereby attenuating pathological progression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70287-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70287","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T07:41:19Z","timestamp":1762328479000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Microglial Morphological Changes and Activation in Chronic Cerebral Hypoperfusion Are Suppressed by Lipid Peroxidation Inhibitor, Methyldopa"],"prefix":"10.1111","volume":"169","author":[{"given":"Ryo","family":"Hagimori","sequence":"first","affiliation":[{"name":"Department of Molecular Pathobiology Faculty of Pharmaceutical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology Faculty of Pharmaceutical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoya","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology Faculty of Pharmaceutical Sciences, Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senri","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of 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