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Methylglyoxal (MG), a highly reactive dicarbonyl, is a shared causative factor associated with cardiovascular and neurological diseases. MG\u2010derived advanced glycation end products (MG\u2010AGEs) accumulate in the heart and circulation post\u2010MI, making it a promising target in studying the heart\u2010brain axis. Here, we report that MG\u2010AGEs accumulate in the mouse brain at 6 h and 7 days post\u2010MI, with the highest expression observed in the brainstem, followed by the cortex. Notably, males had higher MG\u2010AGE expression compared to females in most brain regions. The accumulation of MG\u2010AGEs in the brain was correlated with increased neuroinflammation, including a greater number of activated microglia and macrophages, and increased expression of AGE receptors. Greater inflammatory factor expression (NF\u2010\u03baB and TNF\u2010\u03b1) and a reduction in tight junction proteins of the blood brain barrier were also observed. Taken together, this study reveals a novel MG\u2010mediated mechanism with sex\u2010based differences that may contribute significantly to heart\u2010brain interactions after MI and identifies a promising therapeutic target for treating the neurological impairment associated with heart disease.<\/jats:p>","DOI":"10.1002\/advs.202522584","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T19:39:06Z","timestamp":1775763546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Methylglyoxal Accumulation is Associated with Brain Inflammation after Myocardial Infarction with Sex and Regional Differences"],"prefix":"10.1002","volume":"13","author":[{"given":"Ramis","family":"Ileri","sequence":"first","affiliation":[{"name":"Bioengineering and Therapeutic Solutions (BEaTS) Program University of Ottawa Heart Institute  Ottawa Canada"},{"name":"Ottawa\u2010Carleton Institute For Biomedical Engineering (OCIBME)  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixi","family":"Guo","sequence":"additional","affiliation":[{"name":"Bioengineering and Therapeutic Solutions (BEaTS) Program University of Ottawa Heart Institute  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6470-060X","authenticated-orcid":false,"given":"Erik J.","family":"Suuronen","sequence":"additional","affiliation":[{"name":"Bioengineering and Therapeutic Solutions (BEaTS) Program University of Ottawa Heart Institute  Ottawa Canada"},{"name":"Ottawa\u2010Carleton Institute For Biomedical Engineering (OCIBME)  Ottawa Canada"},{"name":"Department of Cellular and Molecular Medicine University of Ottawa  Ottawa Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892\u2010019\u20101161\u20102"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(16)30677\u20108"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13642"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/4899688"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000476"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184244"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.02.004"},{"key":"e_1_2_10_9_1","first-page":"641","article-title":"Assessment and Treatment of Depression Following Myocardial Infarction","volume":"64","author":"Guck T. 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