TRPV4 antagonists ameliorate ventriculomegaly in a rat model of hydrocephalus
| Autor: | Makenna M. Reed, Bonnie L. Blazer-Yost, Paul R. Territo, Joon W. Shim, Hillary M. Smith, Alexandra E. Hochstetler, Daniel H. Fulkerson, Daniel Preston |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
TRPV4 Morpholines TRPV Cation Channels Therapeutics Pharmacology Nervous System Malformations 03 medical and health sciences Transient receptor potential channel 0302 clinical medicine Cerebrospinal fluid Genetic model Medicine Animals Pyrroles Adverse effect Cerebral Cortex business.industry General Medicine medicine.disease Hydrocephalus Rats Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis Ion channels Osmoregulation business Epithelial transport of ions and water Neurological disorders Ventriculomegaly Research Article Neuroscience |
| Zdroj: | JCI Insight, Vol 5, Iss 18 (2020) JCI Insight |
| ISSN: | 2379-3708 |
| Popis: | Hydrocephalus is a serious condition that impacts patients of all ages. The standards of care are surgical options to divert, or inhibit production of, cerebrospinal fluid; to date, there are no effective pharmaceutical treatments, to our knowledge. The causes vary widely, but one commonality of this condition is aberrations in salt and fluid balance. We have used a genetic model of hydrocephalus to show that ventriculomegaly can be alleviated by inhibition of the transient receptor potential vanilloid 4, a channel that is activated by changes in osmotic balance, temperature, pressure and inflammatory mediators. The TRPV4 antagonists do not appear to have adverse effects on the overall health of the WT or hydrocephalic animals. Two distinct TRPV4 antagonists ameliorate ventriculomegaly in a genetic rat model of severe postnatal hydrocephalus, with no apparent adverse effects on animals. |
| Databáze: | OpenAIRE |
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