CSF Secretion Is Not Altered by NKCC1 Nor TRPV4 Antagonism in Healthy Rats
| Autor: | Daniel Omileke, Neil J. Spratt, Steven W. Bothwell, Adjanie Patabendige |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
choroid plexus business.industry General Neuroscience loop diuretics Antagonist intracranial pressure Neurosciences. Biological psychiatry. Neuropsychiatry Article cerebrospinal fluid Cerebrospinal fluid Endocrinology TRPV4 Cerebral aqueduct Internal medicine NKCC1 Medicine Choroid plexus Secretion business Acetazolamide Antagonism RC321-571 medicine.drug Intracranial pressure |
| Zdroj: | BRAIN SCIENCES Brain Sciences Brain Sciences, Vol 11, Iss 1117, p 1117 (2021) Volume 11 Issue 9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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