Development of Pharmacotherapies for the Treatment of Hydrocephalus
Abstract
The proposed studies aim to test the efficacy and mechanism of action of TRPV4 antagonists for the treatment of hydrocephalus. Whether the cause of hydrocephalus is brain hemorrhage as in pre-term infants, idiopathic normal pressure hydrocephalus of the elderly or post-traumatic hydrocephalus of any age, reducing the production of cerebrospinal fluid (CSF) with a pharmaceutical agent is a promising, novel treatment with the potential to revolutionize clinical outcomes. Preliminary data suggest that TRPV4 antagonists represent such a potential drug treatment. The proposed studies will characterize and use unique rodent models of hydrocephalus to study the efficacy of drug treatment. In addition, cultured choroid plexus (CP) cells will be used to study the mechanisms of action of the drug. In the second year we have made progress in all the proposed second year experiments listed in the SOW. Specifically we have completed the MRI studies to characterize TRPV4 antagonist treatment in pre-weaning animals of the rat model. We have performed behavioral studies in an adult rat-model of the disease. We have done pilot MRI studies in the mice models and are in the process of backcrossing the mice models onto different genetic background to lessen the severity of the disease. The choroid plexus cell line has been used to characterize inflammatory proteins involved in CSF production and these data have been accepted for publication. All of these studies will provide a deeper understanding of the function of the CP and will advance the study of potential drug treatment for hydrocephalus.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2021
- Accession Number
- AD1152598
Entities
People
- Bonnie L. Blazer-yost
Organizations
- Indiana University