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TRPV4 antagonists ameliorate ventriculomegaly in a rat model of hydrocephalus
Alexandra E. Hochstetler, Hillary M. Smith, Daniel C. Preston, Makenna M. Reed, Paul R. Territo, Joon W. Shim, Daniel Fulkerson, Bonnie L. Blazer-Yost
Alexandra E. Hochstetler, Hillary M. Smith, Daniel C. Preston, Makenna M. Reed, Paul R. Territo, Joon W. Shim, Daniel Fulkerson, Bonnie L. Blazer-Yost
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Research Article Neuroscience Therapeutics

TRPV4 antagonists ameliorate ventriculomegaly in a rat model of hydrocephalus

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Abstract

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.

Authors

Alexandra E. Hochstetler, Hillary M. Smith, Daniel C. Preston, Makenna M. Reed, Paul R. Territo, Joon W. Shim, Daniel Fulkerson, Bonnie L. Blazer-Yost

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Figure 3

Representative MRI Scans Before and After Treatment with RN 1734.

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Representative MRI Scans Before and After Treatment with RN 1734.
MRI Im...
MRI Images of P7 and P14 WT (Tmem67+/+), heterozygous (Tmem67+/–), and homozygous/hydrocephalic (Tmem67–/–) rats demonstrating the size of the lateral ventricles before and after treatment with vehicle or RN 1734. The images are shown as coronal, sagittal, and horizontal plane images, and a 3D rendering of the lateral ventricles. Red and green are pseudocolors of the right and left lateral ventricles to provide additional definition of the fluid compartments.

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