Development of Pharmacotherapies for the Treatment of Hydrocephalus
Abstract
It was hypothesized that blocking TRPV4 with selective antagonists would reduce hydrocephalus thus leading to greater preservation of brain structure and function. Specific Aims and Objectives: The original work addressed two independent objectives: 1) testing the efficacy and mechanism of action of TRPV4 antagonists for the treatment of hydrocephalus and 2) characterization of in vivo and in vitro models of hydrocephalus that could be used for future studies aimed at identifying critical pathways and potential drug targets. To address these objectives, there were 5 specific aims to 1) Quantify the effect of TRPV4 antagonist treatment on the hydrocephalic phenotype in three animal models; 2) Quantitate behavioral changes and neuropathological outcomes in a rat model of slowly progressing hydrocephalus and evaluate the therapeutic effectiveness of treatment with TRPV4 antagonists on functional and structural outcomes; 3) Determine the changes in ion transporter expression and localization in vivo during hydrocephalic development and treatment with TRPV4 antagonists; 4) Use the newly developed models to examine the changes in ion transporters that contribute to both normal and excess CSF production; and 5) Compare the subcellular localization of key transport proteins in cultured cells with native tissue.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2022
- Accession Number
- AD1190681
Entities
People
- Bonnie L. Blazer-yost
Organizations
- Indiana University