{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:48:48Z","timestamp":1791308928184,"version":"4.3.1"},"reference-count":26,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515010323"],"award-info":[{"award-number":["2021A1515010323"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515011904"],"award-info":[{"award-number":["2023A1515011904"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neonatal hypoxic\u2013ischemic brain damage (HIBD) is a serious inflammatory injury. At present, the standard treatment for this disease is hypothermia therapy, and the effect of drug intervention is still limited. L\u2010F001 is a compound of fasudil and lipoic acid. Previous in vitro experiments have confirmed that L\u2010F001 has anti\u2010inflammatory neuroprotective functions. However, its therapeutic effect on neonates with HIBD remains unknown. This study was aimed at exploring the therapeutic effect of L\u2010F001 on HIBD rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The newborn rats were divided into three groups: Sham operation group, HIBD group, and HIBD\u00a0+\u00a0L\u2010F001 group. HE staining, Nissil staining, the immunofluorescence of iNOS and COX\u20102, ELISA (IL\u20101\u03b2, IL\u20106, TNF\u2010\u03b1, and IL\u201010), and western blotting analyses were performed to determine the therapeutic effect of L\u2010F001. Finally, we evaluated the growth and development of each group by measuring body weight.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The hippocampal structure of HIBD rats was disordered, and the Nissil body was small and shallow. The expressions of iNOS and COX\u20102 in HIBD rats were increased, whereas the expressions of IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1 in plasma were upregulated, and the expression of IL\u201010 was decreased. L\u2010F001 could improve the tissue structure and reduce the expression of iNOS and COX\u20102 in HIBD rats. Meanwhile, L\u2010F001 could also reduce the expression of pro\u2010inflammatory cytokines and restore the content of anti\u2010inflammatory cytokines in plasma. We further found that the TLR4 pathway was activated after hypoxic\u2010ischemia in neonatal rats. L\u2010F001 could inhibit the activation of TLR4 pathway. Finally, we found that after L\u2010F001 treatment, the body weight of HIBD rats increased significantly compared with the untreated group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>L\u2010F001 antagonizes the inflammatory response after hypoxic\u2010ischemia by inhibiting the activation of the TLR4 signaling pathway, thus playing a neuroprotective role. L\u2010F001 may be a potential therapeutic agent for neonatal HIBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.3280","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T02:37:56Z","timestamp":1697078276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["L\u2010F001, a multifunctional fasudil\u2013lipoic acid dimer, antagonizes hypoxic\u2013ischemic brain damage by inhibiting the TLR4\/MyD88 signaling pathway"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3505-4829","authenticated-orcid":false,"given":"Ruiyu","family":"Zhou","sequence":"first","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"The Affiliated Kashi Hospital Sun Yat\u2010sen University  Kashi 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