2025/09/15 by Cong Dai, Qing Nan, Menglu Xu +1 · 1 voice
Medicine · Neuroscience · #Anesthesia and Neurotoxicity Research #Anesthesia and Sedative Agents #Intensive Care Unit Cognitive Disorders
paper · doi:10.1002/nep3.70015
openalex publication_date 2025/09/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25
Abstract Postoperative delirium (POD), a prevalent neurological complication in older surgical patients, adversely affects recovery. Isoflurane, a common inhalational anesthetic, exhibits neurotoxic potential, but its role in POD pathogenesis remains unclear. Network toxicology and molecular docking strategies identified 38 shared targets between isoflurane (PubChem/ChEMBL) and POD (GeneCards). Protein‐protein interaction networks (STRING/Cytoscape) screened eight core genes: catechol‐O‐methyltransferase ( COMT ), angiotensin l‐converting enzyme ( ACE ), solute carrier family 6, member 3 ( SLC6A3 ), cathepsin B ( CTSB ), apoptosis‐related cysteine peptidase ( CASP3 ), B‐lymphoblastoma‐2 gene ( BCL‐2 ), coagulation factor VII ( F7 ), and nuclear receptor subfamily 3 ( NR3C1 ). Functional enrichment (Gene Ontology [GO]/Kyoto Encyclopedia of Genes and Genomes [KEGG]) analyzed biological pathways. Key pathways implicated include calcium signaling, dopamine/catecholamine synaptic uptake, cholinergic synapses, endocrine resistance, and estrogen signaling. Molecular docking confirmed strong binding affinity between isoflurane and core targets (e.g., CASP3 : affinity–5.54 kcal/mol), highlighting dopaminergic disruption and apoptotic activation. This study elucidates isoflurane's multi‐target neurotoxicity in POD, providing a mechanistic foundation for mitigating postoperative neurological complications.