{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:44:57Z","timestamp":1777383897156,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of University and Research"},{"DOI":"10.13039\/501100005389","name":"University of Insubria","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005389","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intestinal ischemia and reperfusion injury (IRI) can lead to multiple organ dysfunction, including the central nervous system (CNS), where a neuroinflammatory response may develop. Hyaluronan, a glycosaminoglycan component of the extracellular matrix, has been shown to modulate enteric neuronal and immune function during in vivo IRI in the rat small intestine. The aim of this study was to investigate the potential involvement of hyaluronan in the alterations induced by in vivo intestinal IRI in the rat hippocampus and striatum. Mesenteric ischemia was induced in anesthetized adult male rats for 60 min, followed by 24 h of reperfusion. Injured (IRI group), sham-operated (SHAM group), and non-injured (CTR group) animals were treated with the hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU; 25 mg\/kg). In the hippocampus and striatum of the IRI group, levels of both hyaluronan and neurocan, a proteoglycan primarily found in the central nervous system extracellular matrix, as well as the hyaluronan synthesizing enzyme Has2, were significantly downregulated compared to the CTR and SHAM groups. These changes were associated with alterations in the TLR4-NF\u03baB-pI\u03baB pathway, with the effects being more prominent in the hippocampus than in the striatum. Increased levels of IL6, co-localizing with the microglial marker S100\u03b2, were observed in both regions and were attenuated by 4-MU only in the hippocampus. Overall, these findings suggest that intestinal IRI may disrupt extracellular matrix homeostasis and induce hyaluronan-mediated enhancement of local proinflammatory signaling, primarily involving IL6 and microglial cells, mainly in the hippocampus. Such changes may contribute to the development of cognitive deficits and memory dysfunction associated with intestinal IRI.<\/jats:p>","DOI":"10.3390\/ijms262010064","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T12:17:02Z","timestamp":1760617022000},"page":"10064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intestinal Ischemia\/Reperfusion Injury Influences Hyaluronan Homeostasis in the Rat Brain"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5027-880X","authenticated-orcid":false,"given":"Annalisa","family":"Bosi","sequence":"first","affiliation":[{"name":"Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6996-4797","authenticated-orcid":false,"given":"Nicol\u00f2","family":"Baranzini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Life Sciences, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4917-6706","authenticated-orcid":false,"given":"Alessandra","family":"Ponti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Technological Innovation, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Moretto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Moro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Crema","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5378-8442","authenticated-orcid":false,"given":"Rossella","family":"Cianci","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy"},{"name":"Fondazione Policlinico Universitario A. 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