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Integrating network toxicology, machine learning, transcriptomics, immune infiltration, molecular docking\/dynamics, single-cell RNA sequencing, and in vivo\/ in vitro experiments, we identified 264 DEHP\u2013SAH overlapping targets enriched in PI3K-Akt\/MAPK pathways. Three core genes (ADORA1, PDGFRA, PTGS2) were screened, with ADORA1 specifically upregulated in astrocytes under SAH. Chronic DEHP exposure exacerbated neurological deficits, neuronal damage, astrocyte proliferation\/activation, apoptosis, and inflammatory cytokines in SAH mice, while reducing antioxidant enzymes. In primary astrocytes, DEHP suppressed viability, activated PI3K-Akt\/MAPK, and induced oxidative stress and inflammation, synergizing with Hemin. An adverse outcome pathway framework was constructed. These findings reveal that DEHP aggravates SAH neurotoxicity via ADORA1-mediated astrocyte inflammation and oxidative stress through the PI3K-Akt\/MAPK axis, providing new insights into environmental pollutant neurotoxicity.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05550","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:11:15Z","timestamp":1785849075000},"page":"23795-23815","source":"Crossref","is-referenced-by-count":0,"title":["Di(2-ethylhexyl)\nPhthalate (DEHP) Exposure Exacerbates\nSubarachnoid Hemorrhage by Inducing Astrocyte-Mediated Inflammation\nand Oxidative Stress through the ADORA1\/PI3K-Akt\/MAPK Axis"],"prefix":"10.1021","volume":"74","author":[{"given":"Shaojie","family":"Li","sequence":"first","affiliation":[{"name":"The Second Affiliated Clinical Medical College of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]},{"name":"The Second Affiliated Hospital of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofang","family":"Wu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Clinical Medical College of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]},{"name":"The Second Affiliated Hospital of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0488-8547","authenticated-orcid":true,"given":"Jianjin","family":"Guo","sequence":"additional","affiliation":[{"name":"Lanzhou University , , ,","place":["Lanzhou, China, 730000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanxi Medical University , , ,","place":["Taiyuan, China, 030001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longjie","family":"Chen","sequence":"additional","affiliation":[{"name":"The Second Affiliated Clinical Medical College of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]},{"name":"The Second Affiliated Hospital of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanglu","family":"Lin","sequence":"additional","affiliation":[{"name":"The Second Affiliated Clinical Medical College of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]},{"name":"The Second Affiliated Hospital of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Clinical Medical College of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]},{"name":"The Second Affiliated Hospital of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-3451","authenticated-orcid":true,"given":"Hongzhi","family":"Gao","sequence":"additional","affiliation":[{"name":"The Second Affiliated Clinical Medical College of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]},{"name":"The Second Affiliated Hospital of Fujian Medical University , , ,","place":["Quanzhou, China, 362000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"2026080510105182800_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2022.157443","article-title":"Adverse Cardiovascular Effects and\nPotential Molecular Mechanisms of DEHP and Its Metabolites-A Review","volume":"847","author":"Wen","year":"2022","journal-title":"Sci. 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