{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T07:25:11Z","timestamp":1787037911903,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFF0724900"],"award-info":[{"award-number":["2023YFF0724900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Conventional tribromoethanol anesthesia is compromised by solvent\u2010related toxicity, limiting its utility in prolonged experimental protocols. We hypothesized that reformulation with 1,2\u2010propanediol could improve its biosafety while revealing its potential mechanism of action in the central nervous system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo biocompatibility was evaluated using OECD\u2010standard irritation models, while anesthetic efficacy was quantitatively determined via the up\u2013down sequential allocation method, complemented by tail\u2010immersion and writhing tests to characterize antinociceptive effects. Moreover, physiological stability was monitored using non\u2010invasive tail\u2010cuff plethysmography and rectal thermometry for cardiovascular and core temperature assessment. In addition, subacute toxicity was assessed through repeated dosing, and MRI for neurostructural integrity. Finally, cognitive function and mechanisms were probed via the Morris water maze, molecular docking, region\u2010specific protein expression, and real\u2010time cerebral oxygen saturation mapping using photoacoustic imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The 1,2\u2010propanediol formulation markedly reduced local tissue irritation and improved pulse\u2010rate, blood\u2010pressure, thermoregulatory, and repeated\u2010dosing survival profiles compared with the conventional 2\u2010methyl\u20102\u2010butanol formulation. TBE\/PG exhibited dose\u2010dependent anesthetic efficacy without significant strain\u2010 or sex\u2010associated differences. Repeated administration induced transient spatial learning impairment and reduced cerebral oxygen saturation; these effects were largely reversible after drug withdrawal and retraining. Molecular docking and regional protein profiling identified GABRA1, which was enriched in the pons, as a candidate mechanistic correlate of TBE\u2010induced anesthesia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study establishes a biocompatible TBE formulation as a superior injectable anesthetic with enhanced safety and reversible cognitive effects. The results pinpoint pontine GABRA1 targeting as a novel pathway for TBE\u2010induced anesthesia, providing a robust framework for refining preclinical sedation protocols and future neurotoxicological evaluations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70265","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:34:32Z","timestamp":1787034872000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["1,2\u2010propanediol reformulation improves tribromoethanol safety and reveals pontine\n                    <scp>GABRA1<\/scp>\n                    enrichment as a candidate mechanistic correlate of anesthesia"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9252-0189","authenticated-orcid":false,"given":"Xia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Science Peking University  Beijing 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