{"id":4793,"date":"2021-04-14T22:29:58","date_gmt":"2021-04-15T02:29:58","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/tspo-pet-detects-acute-neuroinflammation-but-not-diffuse-chronically-activated-mhcii-microglia-in-the-rat-2\/"},"modified":"2024-12-03T14:57:41","modified_gmt":"2024-12-03T19:57:41","slug":"tspo-pet-detects-acute-neuroinflammation-but-not-diffuse-chronically-activated-mhcii-microglia-in-the-rat-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/tspo-pet-detects-acute-neuroinflammation-but-not-diffuse-chronically-activated-mhcii-microglia-in-the-rat-2\/","title":{"rendered":"TSPO PET detects acute neuroinflammation but not diffuse chronically activated MHCII microglia in the rat"},"content":{"rendered":"<h2 class=\"title\">Abstract<\/h2>\n<div id=\"enc-abstract\" class=\"abstract-content selected\">\n<p><strong class=\"sub-title\">Background:\u00a0<\/strong>Accurate and sensitive imaging biomarkers are required to study the progression of white matter (WM) inflammation in neurodegenerative diseases. Radioligands targeting the translocator protein (TSPO) are considered sensitive indicators of neuroinflammation, but it is not clear how well the expression of TSPO coincides with major histocompatibility complex class II (MHCII) molecules in WM. This study aimed to test the ability of TSPO to detect activated WM microglia that are immunohistochemically positive for MHCII in rat models of prodromal Alzheimer&rsquo;s disease and acute subcortical stroke.<\/p>\n<p><strong class=\"sub-title\">Methods:\u00a0<\/strong>Fischer 344 wild-type (n = 12) and TgAPP21 (n = 11) rats were imaged with [<sup>18<\/sup>F]FEPPA PET and MRI to investigate TSPO tracer uptake in the corpus callosum, a WM region known to have high levels of MHCII activated microglia in TgAPP21 rats. Wild-type rats subsequently received an endothelin-1 (ET1) subcortical stroke and were imaged at days 7 and 28 post-stroke before immunohistochemistry of TSPO, GFAP, iNOS, and the MHCII rat antigen, OX6.<\/p>\n<p><strong class=\"sub-title\">Results:\u00a0<\/strong>[<sup>18<\/sup>F]FEPPA PET was not significantly affected by genotype in WM and only detected increases near the ET1 infarct (P = 0.033, infarct\/cerebellum uptake ratio: baseline = 0.94 \u00b1 0.16; day 7 = 2.10 \u00b1 0.78; day 28 = 1.77 \u00b1 0.35). Immunohistochemistry confirmed that only the infarct (TSPO cells\/mm<sup>2<\/sup>: day 7 = 555 \u00b1 181; day 28 = 307 \u00b1 153) and WM that is proximal to the infarct had TSPO expression (TSPO cells\/mm<sup>2<\/sup>: day 7 = 113 \u00b1 93; day 28 = 5 \u00b1 7). TSPO and iNOS were not able to detect the chronic WM microglial activation that was detected with MHCII in the contralateral corpus callosum (day 28 OX6% area: saline = 0.62 \u00b1 0.38; stroke = 4.30 \u00b1 2.83; P = .029).<\/p>\n<p><strong class=\"sub-title\">Conclusion:\u00a0<\/strong>TSPO was only expressed in the stroke-induced insult and proximal tissue and therefore was unable to detect remote and non-insult-related chronically activated microglia overexpressing MHCII in WM. This suggests that research in neuroinflammation, particularly in the WM, would benefit from MHCII-sensitive radiotracers.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4793","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>TSPO PET detects acute neuroinflammation but not diffuse chronically activated MHCII microglia in the rat - CCNA - CCNV<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/tspo-pet-detects-acute-neuroinflammation-but-not-diffuse-chronically-activated-mhcii-microglia-in-the-rat-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"TSPO PET detects acute neuroinflammation but not diffuse chronically activated MHCII microglia in the rat - 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