title: Propofol administration modulates AQP-4 expression and brain edema after traumatic brain injury.
abstract: The increased intracranial pressure caused by brain edema following traumatic brain injury (TBI) always leads to poor patient prognosis. Aquaporin-4 (AQP-4) plays an important role in edema formation and resolution, which may provide a novel therapeutic target for edema treatment. In this present study, we found that propofol treatment, within a short time, after TBI significantly reduced brain edema in a controlled cortical injury rat model and suppressed in vivo expression of AQP-4. The ameliorating effect of propofol was associated with attenuated expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, the regulatory effect of propofol on AQP-4 expression was investigated in cultured astrocytes. Results showed that propofol could block the stimulatory effect of IL-1β and TNF-α on AQP-4 expression in cultured astrocytes. We also found that both NFκB and p38/MAPK pathways were involved in IL-1β and TNF-α-induced AQP-4 expression and that propofol functions as a dual inhibitor of NFκB and p38/MAPK pathways. In conclusion, treatment with propofol, within a short time, after TBI attenuates cerebral edema and reduces the expression of AQP-4. Propofol modulates acute AQP-4 expression by attenuating IL-1β and TNF-α expression and inhibiting IL-1β and TNF-α induced AQP-4 expression.
authors.affiliation: Emergency Center, The Affiliated Wuxi People's Hospital, Nanjing Medical University, Wuxi, 214023, China, drzyding@gmail.com.
authors.forename: Zhongyang
authors.initials: Z
authors.lastname: Ding
authors.forename: Jiaming
authors.initials: J
authors.lastname: Zhang
authors.forename: Jinyu
authors.initials: J
authors.lastname: Xu
authors.forename: Guangjie
authors.initials: G
authors.lastname: Sheng
authors.forename: Guorong
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics* / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D015742:Propofol / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D051401:Aquaporin 4; D053583:Interleukin-1beta; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D015742:Propofol