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Such postoperative cognitive deficits are dependent on the presence of microglia in the brain, which, when activated, trigger neuroinflammation. The objective of our study was to determine whether modulation of \u03b15\u2010GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors by the \u03b15\u2010positive allosteric modulator (\u03b15\u2010PAM), MP\u2010III\u2010022, would improve cognitive deficits after surgery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      MP\u2010III\u2010022 (1\u2009mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7day\n                      <jats:sup>\u22121<\/jats:sup>\n                      in the drinking water) was administered to mice 3\u2009days prior to laparotomy and throughout the study. Chronologically aged mice (21\u201324\u2009months old) and mice with ablation of dentate gyrus hilar somatostatin interneurons (4\u20135\u00a0months old), a model for hippocampal ageing, were used. Cognitive functions were assessed using a battery of behavioural tests. Immunohistochemistry and Golgi staining were used to analyse microglial activation and dendritic spine density.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>In both types of mice, we found that laparotomy reduced the percentage of spontaneous alternations in the Y maze, novel object recognition, and contextual fear conditioning, while these deficits were attenuated with MP\u2010III\u2010022 treatment, indicating prevention or reversal of postoperative cognitive impairments. Laparotomy increased hippocampal microglial activation\u2010associated measures and reduced dendritic spine density, and these changes were attenuated by MP\u2010III\u2010022 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>\n                      The \u03b15\u2010PAM, MP\u2010III\u2010022, essentially abolished laparotomy\u2010induced cognitive deficits and structural alterations. Positive allosteric modulation of \u03b15\u2010GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors may represent a novel therapeutic strategy to prevent the development of perioperative neurocognitive deficits in aged individuals.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70474","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:16:57Z","timestamp":1778653017000},"page":"4836-4854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevention of microglial activation and postoperative cognitive deficits by positive allosteric modulation of \u03b15\u2010GABA\n                    <sub>A<\/sub>\n                    receptors"],"prefix":"10.1111","volume":"183","author":[{"given":"Jinrui","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Comparative Biosciences College of Veterinary Medicine, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"},{"name":"Neuroscience Program College of Liberal Arts &amp; Sciences, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajasekar","family":"Nagarajan","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences College of Veterinary Medicine, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dishary","family":"Sharmin","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prithu","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maltesh","family":"Kambali","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences College of Veterinary Medicine, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muxiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences College of Veterinary Medicine, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"},{"name":"Neuroscience Program College of Liberal Arts &amp; Sciences, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences College of Veterinary Medicine, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"},{"name":"Neuroscience Program College of Liberal Arts &amp; Sciences, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences College of Veterinary Medicine, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"},{"name":"Neuroscience Program College of Liberal Arts &amp; Sciences, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"},{"name":"Beckman Institute for Advanced Science and Technology University of Illinois Urbana\u2010 Champaign  Urbana Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9396-4746","authenticated-orcid":false,"given":"Uwe","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Department of Comparative Biosciences College of Veterinary Medicine, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"},{"name":"Neuroscience Program College of Liberal Arts &amp; Sciences, University of Illinois Urbana\u2010Champaign  Urbana Illinois USA"},{"name":"Carl R. 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