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Development of Pharmacotherapies for the Treatment of Hydrocephalus

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[Technical Report, Annual Report]

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The proposed studies aim to test the efficacy and mechanism of action of TRPV4 antagonists for the treatment of hydrocephalus in rodent models. 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 first year we have made progress in all the proposed first year experiments listed in the SOW. Specifically we have further characterized a rat model of the disease and have performed TRPV4 antagonist treatment in pre-weaning animals. We are in the process of performing behavioral studies in an adult rat model of the disease and correlating these with disease severity. Finally the CP cell line has been used to characterize regulation of important transport proteins involved in CSF production. 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.

Subject Categories:

  • Medicine and Medical Research
  • Anatomy and Physiology

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[A, Approved For Public Release]