{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:54:19Z","timestamp":1781589259698,"version":"3.54.5"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Hum. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Heat stress (HS) can progress to heat stroke, a life-threatening condition. Aquaporin-4 (AQP4) has been implicated in HS-induced brain injury, but its role in heat acclimation (HA)-mediated protection remains unclear. This study investigated whether HA ameliorates HS-induced brain damage through AQP4.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>9L\/lacZ cells were randomly assigned to four groups: Control (37\u202f\u00b0C, 5% CO\u2082), HA (39\u202f\u00b0C, 5% CO\u2082, 2\u202fh\/day for 6\u202fdays), HS (43\u202f\u00b0C, 5% CO\u2082, 2\u202fh), and HA+HS (HA pretreatment followed by HS). In addition, cells in the Control and HS groups were treated with the selective AQP4 inhibitor TGN-020 (0.1\u202f\u03bcmol\/mL, 2\u202fh before HS). The expression of HSP70, HSP90, and AQP4 was measured by western blotting; AQP4 mRNA levels were assessed by RT-PCR. Cell proliferation viability was evaluated by CCK-8 assay, and apoptosis was detected by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Notably, AQP4 expression (RT-PCR and Western blot) was lower in the HA+HS group than in the HS group. Flow cytometry revealed that both HA+HS and TGN-020 treatment reduced apoptosis compared with HS alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings indicate that HA attenuates HS-induced injury by downregulating AQP4 expression, and that AQP4 inhibition mimics this protective effect. AQP4 represents a potential therapeutic target for heat stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnhum.2026.1830585","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:39:24Z","timestamp":1781588364000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of AQP4 in ameliorating heat stress-induced cellular injury in a cell line model through active heat acclimation"],"prefix":"10.3389","volume":"20","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Emergency, Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuhan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The 71st Group Army Hospital of CPLA Army","place":["Xuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing University of Chinese Medicine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhua","family":"Cao","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The Fifth Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Emergency, Third Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhen","family":"Ma","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1097\/00004647-200204000-00001","article-title":"Aquaporins in brain: distribution, physiology, and pathophysiology","volume":"22","author":"Badaut","year":"2002","journal-title":"J. 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