- Title
- CSF Secretion Is Not Altered by NKCC1 Nor TRPV4 Antagonism in Healthy Rats
- Creator
- Bothwell, Steven W.; Omileke, Daniel; Patabendige, Adjanie; Spratt, Neil J.
- Relation
- NHMRC.APP1085450 http://purl.org/au-research/grants/nhmrc/1085450
- Relation
- Brain Sciences Vol. 11, Issue 9, no. 1117
- Publisher Link
- http://dx.doi.org/10.3390/brainsci11091117
- Publisher
- MDPI AG
- Resource Type
- journal article
- Date
- 2021
- Description
- 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.
- Subject
- cerebrospinal fluid; choroid plexus; NKCC1; TRPV4; intracranial pressure; loop diuretics
- Identifier
- http://hdl.handle.net/1959.13/1438566
- Identifier
- uon:40649
- Identifier
- ISSN:2076-3425
- Rights
- © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
- Language
- eng
- Full Text
- Reviewed
- Hits: 1167
- Visitors: 1257
- Downloads: 96
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version | 1 MB | Adobe Acrobat PDF | View Details Download |