{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:52:03Z","timestamp":1791492723502,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Traumatic brain injury (TBI) causes a high level of blood glutamate, which triggers host defense by activating oxidative stress and inflammation response. However, the concrete mechanism underlying its exacerbating effects on acute lung injury (ALI) severity remains unknown. In the present study, we aim to demonstrate the special role of N\u2010methyl\u2010D\u2010aspartate receptor (NMDAR) in regulating glutamate\u2010related inflammation signaling to facilitate the sustaining injury. After the interventions, blood glutamate concentration was measured using HPLC\u2010MS\/MS. The level of pro\u2010inflammation cytokines, wet\/dry weight ratio, protein concentration, and lung injury score were measured to examine the severity of lung damage. The oxidative status was evaluated by measuring the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) activity, and intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    concentration. Endothelial cell dysfunction was assessed through dye extravasation assay and quantification of p\u2010NFAT, p\u2010p65, ICAM\u20101, and VCAM\u20101 expression levels. Results showed that glutamate activated the NMDAR pathway, inducing endothelial barrier dysfunction via ROS\/MDA elevation and SOD suppression. This cascade promoted the concentration of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , activating both nuclear factor of activated T cells (NFAT) and nuclear factor kappa\u2010B (NF\u2010\u03baB) pathway. Glutamate administration exacerbated NMDAR activation, leading to persistent lung injury following TBI. Memantine\u2010mediated NMDAR blockade effectively attenuated this injury. Our findings indicate that blood glutamate elevation may trigger TBI\u2010associated acute lung injury (TBI\u2010ALI) through endothelial NMDAR\/ROS\/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling.\n                  <\/jats:p>","DOI":"10.1002\/kjm2.70087","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:43:58Z","timestamp":1757501038000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Glutamate Exacerbates Traumatic Brain Injury\u2010Induced Acute Lung Injury Through\n                    <scp>NMDAR<\/scp>\n                    \/\n                    <scp>ROS<\/scp>\n                    \/Ca\n                    <sup>2+<\/sup>\n                    Signaling Pathway in Pulmonary Endothelial Cells"],"prefix":"10.1002","volume":"41","author":[{"given":"Song","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery Ningbo Medical Center Lihuili Hospital  Ningbo Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2621-1017","authenticated-orcid":false,"given":"Ying\u2010Ying","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Pain Ningbo Medical Center Lihuili Hospital  Ningbo Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010Zhen","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Ningbo Medical Center Lihuili Hospital  Ningbo Zhejiang Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4037\/aacnacc2021331"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-023-02484-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms\/174264"},{"issue":"3","key":"e_1_2_8_5_1","article-title":"The Role of Glutamate Receptors in Epilepsy","volume":"11","author":"Chen T. 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