en Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background:</span></span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">This study aimed to investigate the regulatory mechanisms of brain microvascular endothelial cell (BMEC) permeability, with a focus on the role of Kir2.1 (KCNJ2) potassium channels and their potential interaction with ionizing radiation (IR). </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Materials and Methods: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">BMECs were isolated from seven-day-old Sprague-Dawley rats, and cells were stimulated with lipopolysaccharide (LPS) to evaluate inflammatory responses. A 6-MV linear accelerator was used to deliver single radiation doses (0&ndash;8 Gy) to confluent BMEC monolayers to simulate clinical radiotherapy conditions. RhoA activity, p115RhoGEF expression, and tight junction (TJ) proteins (ZO-1, occludin, claudin-5) were detected by Western blotting. Transendothelial electrical resistance (TEER) was used to assess changes in barrier permeability. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Results: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">LPS stimulation significantly increased p115RhoGEF expression at 1, 3, and 6 h compared with the control (P<0.05). TEER values decreased progressively after LPS exposure, indicating impaired barrier integrity (P<0.05). Claudin-5 levels showed no significant change, whereas ZO-1 and occludin were markedly reduced at 6 h and 12 h (P<0.05). Radiation exposure produced similar permeability-enhancing effects, supporting shared mechanisms of barrier disruption. </span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Conclusion: </span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="language:en-US">LPS-induced inflammation increases BMEC permeability primarily through downregulation of TJ proteins. Ionizing radiation produces comparable barrier-disruptive effects, suggesting overlapping regulatory pathways. These findings support a potential role for Kir2.1 channels in modulating BMEC permeability under both inflammatory and radiation-induced stress.</span></span></span></span></span></span></span></span></span></div> Brain microvascular endothelial cells, blood–brain barrier, ionizing radiation, kir2.1 potassium channels, endothelial permeability. 679 684 http://ijrr.com/browse.php?a_code=A-10-1-1563&slc_lang=en&sid=1 L. Deng 7900319475328460034269 7900319475328460034269 No The Department of Neurology, Affiliated Hospital of Jianghan University, Wuhan 430015, Hubei Province, China D. Wu 13476028179@163.com 7900319475328460034270 7900319475328460034270 Yes The Department of Neurology, Affiliated Hospital of Jianghan University, Wuhan 430015, Hubei Province, China