{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:09:33Z","timestamp":1791839373296,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T00:00:00Z","timestamp":1729814400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101424"],"award-info":[{"award-number":["82101424"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hydrocephalus is characterized by secretion, circulation, and absorption disorder of cerebrospinal fluid (CSF) with high morbidity and complication rate. The relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) had received more attention. In this study, we aim to detect the role of Toll\u2010like receptor 4\/nuclear factor\u2010kappa B\/Na+\/K+\/2Cl\u2010cotransporter 1(TLR4\/NF\u2010\u03baB\/NKCC1) signal pathway in the development of hydrocephalus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Hydrocephalus was induced in adult rats (8\u2009weeks) by intracisternal kaolin injection, then pyrrolidinedithiocarbamate (PDTC) and bumetanide were administrated to the rats mode. Then the rat model was evaluated, and ventricular volume was calculated at different time points. Then CPE, cortex, preventricular tissue, and CSF were obtained. Protein expressions of TLR\u20104, NKCC\/serine\u2013threonine STE20\/SPS1\u2010related, proline\u2010alanine\u2010rich kinase (SPAK), pNKCC1, pSPAK, GFAP, AQP1, and AQP4 were measured by RT\u2010PCR, western blot, and immunofluorescence (IF) stains in CPE, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Our data showed that inflammation factors tumor necrosis factor\u2010(TNF\u2010\u03b1), interleukin 18(IL\u201018), and glial fibrillary acidic protein (GFAP) concentrations were significantly higher in the model group than in controls. The TLR4\/NF\u2010\u03baB\/NKCC1 signal pathway were actived by NF\u2010\u03baB\u2010p65, NKCC1, pNKCC1\u2010 pSPAK complex, and Aquaporin1 (AQP1) high expression. PDTC and bumetanide use can help regular TLR4\/NF\u2010\u03baB\/NKCC1 expression and reduced AQP1 expression by down\u2010regulate NF\u2010B\u2010p65 and inhibiting NKCC1, respectively. As a result, the treatment groups alleviated CPE abnormal secretion and ventricle enlargement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results confirmed that the inflammatory reaction contributes TLR4\/NF\u2010\u03baB\/NKCC1 mediated CPE abnormal secretion and consequent hydrocephalus. Regulation of TLR4\/NF\u2010\u03baB\/NKCC1 and AQP1 can prevent this process. Our study provides a strong rationale for further exploring alleviating CPE abnormal secretion as a therapeutic perspective of hydrocephalus.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70085","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T08:39:53Z","timestamp":1729845593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Evaluation of the Choroid Plexus Epithelium Inflammation\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    \/\n                    <scp>NKCC1<\/scp>\n                    Signal Pathway Activation in the Development of Hydrocephalus"],"prefix":"10.1111","volume":"30","author":[{"given":"Hao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Xiamen University School of Medicine, Xiamen University  Xiamen Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of High Magnetic Field and Ion Beam Physical Biology Hefei Institutes of Physical Science, CAS  Hefei Anhui P. R. China"},{"name":"Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology Hefei Institutes of Physical Science, CAS  Hefei Anhui P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine University of Science and Technology of China  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0321-y"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2020.1752182"},{"issue":"404","key":"e_1_2_13_4_1","first-page":"9","article-title":"A Glucagon\u2010Like Peptide\u20101 Receptor Agonist Reduces Intracranial Pressure in a Rat Model of Hydrocephalus","volume":"23","author":"Botfield H. 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