{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T21:29:18Z","timestamp":1776288558693,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071220"],"award-info":[{"award-number":["82071220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371205"],"award-info":[{"award-number":["82371205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Sevoflurane can aggravate the progression of neurodegeneration, although the underlying mechanisms remain incompletely understood. Our previous study identified a link between heterogeneous nuclear ribonucleoprotein A2\/B1 (hnRNPA2\/B1) and sevoflurane\u2010induced neurocognitive impairments. The abnormal hydrogel phase transition of stress granules (SGs) assembled via liquid\u2013liquid phase separation (LLPS) by hnRNPA2\/B1 is a crucial element in neurodegeneration. Karyopherin\u2010\u03b22 (Kap\u03b22) is known to specifically recognize hnRNPA2\/B1 and reverses the hydrogel transition of SGs. This study aimed to elucidate the mechanistic role of hnRNPA2\/B1\u2013SG phase transition in sevoflurane\u2010induced hippocampal neuronal dysfunction under hypoxic conditions, and to determine whether Kap\u03b22 can mitigate these effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a hypoxic primary rat hippocampal neuron model and Kap\u03b22 overexpression, we investigated the effects of sevoflurane on hnRNPA2\/B1 expression and subcellular distribution, phase separation dynamics, and the liquid\u2010to\u2010solid transition of hnRNPA2\/B1\u2010associated SGs. We also assessed neuronal function and cognitive protein expression. Experimental approaches included Western blotting, RT\u2010qPCR, immunofluorescence staining, and fluorescence recovery after photobleaching (FRAP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In hypoxic hippocampal neurons, sevoflurane altered the nuclear\u2010to\u2010cytoplasmic distribution of hnRNPA2\/B1, promoted abnormal LLPS, and facilitated the formation of irreversible solid\u2010phase hnRNPA2\/B1\u2010containing SGs. These changes were associated with neuronal dysfunction and reduced expression of cognition\u2010related proteins. Kap\u03b22 overexpression disrupted these aggregates, restored the dynamic reversibility of hnRNPA2\/B1 LLPS, reversed the sevoflurane\u2010induced hydrogel phase transition of hnRNPA2\/B1\u2010SGs, and enhanced the expression of cognition\u2010related proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The hydrogel phase transition of hnRNPA2\/B1\u2010SG is a key pathological mechanism of sevoflurane\u2010induced hippocampal neuronal injury. Kap\u03b22 may serve as a potential therapeutic target to counteract sevoflurane\u2010related neurotoxicity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70532","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T04:29:24Z","timestamp":1754627364000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kap\u03b22 Reverses Sevoflurane\u2010Induced Hydrogel Phase Transition of hnRNPA2\/B1\u2010SG in Hypoxic Primary Rat Hippocampal Neurons"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2510-2150","authenticated-orcid":false,"given":"Miao","family":"Zhang","sequence":"first","affiliation":[{"name":"The Third Central Clinical College of Tianjin Medical University  Tianjin China"},{"name":"Nankai University Affinity the Third Central Hospital  Tianjin China"},{"name":"Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial 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