{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T04:21:59Z","timestamp":1785558119993,"version":"3.56.0"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT APP1085450"],"award-info":[{"award-number":["GNT APP1085450"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1110629"],"award-info":[{"award-number":["GNT1110629"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008810","name":"NSW Ministry of Health","doi-asserted-by":"publisher","award":["NSW Health Early-Mid Career Fellowship"],"award-info":[{"award-number":["NSW Health Early-Mid Career Fellowship"]}],"id":[{"id":"10.13039\/501100008810","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"publisher","award":["100827"],"award-info":[{"award-number":["100827"]}],"id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Cerebrospinal fluid (CSF) secretion can be targeted to reduce elevated intracranial pressure (ICP). Sodium-potassium-chloride cotransporter 1 (NKCC1) antagonism is used clinically. However, supporting evidence is limited. The transient receptor potential vanilloid-4 (TRPV4) channel may also regulate CSF secretion and ICP elevation. We investigated whether antagonism of these proteins reduces CSF secretion. Methods: We quantified CSF secretion rates in male Wistar rats. The cerebral aqueduct was blocked with viscous mineral oil, and a lateral ventricle was cannulated. Secretion rate was measured at baseline and after antagonist administration. Acetazolamide was administered as a positive control to confirm changes in CSF secretion rates. Results: Neither NKCC1, nor TRPV4 antagonism altered CSF secretion rate from baseline, n = 3, t(2) = 1.14, p = 0.37, and n = 4, t(3) = 0.58, p = 0.6, respectively. Acetazolamide reduced CSF secretion by ~50% across all groups, n = 7, t(6) = 4.294, p = 0.005. Conclusions: Acute antagonism of NKCC1 and TRPV4 proteins at the choroid plexus does not reduce CSF secretion in healthy rats. Further investigation of protein changes and antagonism should be explored in neurological disease where increased CSF secretion and ICP are observed before discounting the therapeutic potential of protein antagonism at these sites.<\/jats:p>","DOI":"10.3390\/brainsci11091117","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:12:22Z","timestamp":1629843142000},"page":"1117","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["CSF Secretion Is Not Altered by NKCC1 Nor TRPV4 Antagonism in Healthy Rats"],"prefix":"10.3390","volume":"11","author":[{"given":"Steven W.","family":"Bothwell","sequence":"first","affiliation":[{"name":"The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8636-3694","authenticated-orcid":false,"given":"Daniel","family":"Omileke","sequence":"additional","affiliation":[{"name":"The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1550-3084","authenticated-orcid":false,"given":"Adjanie","family":"Patabendige","sequence":"additional","affiliation":[{"name":"The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"},{"name":"Institute of Infection, Veterinary & Ecological Sciences, University of Liverpool, Wirral CH64 7TE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil J.","family":"Spratt","sequence":"additional","affiliation":[{"name":"The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW 2308, Australia"},{"name":"Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"},{"name":"Hunter New England Local Health District, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-12-802395-2.00005-5","article-title":"Cerebrospinal fluid circulation and hydrocephalus","volume":"145","author":"Leinonen","year":"2017","journal-title":"Handb. 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