Advance in PIP2 treatment to restore capillary blood flow
Awardee: Fabrice Dabertrand
Institution: University of Colorado Anschutz Medical Campus
Grant Amount: $117,734
Funding Period: February 1, 2023 - January 31, 2024
Summary:
Neurons in the brain have few energy reserves and therefore depend on local blood flow through arterioles and capillaries for a continuous supply of nutrients. A deficit in cerebral blood flow hemodynamics is an early feature of CADASIL, which suggests that cerebrovascular dysfunction has a key role in the pathogenesis leading to dementia. We recently discovered how to rescue the coupling between neuronal activity and local blood flow regulation using a phospholipid-based treatment with PIP2. However, PIP2 can act on several targets, including as an inhibitor of TRPV4 channels, an important player in capillary blood flow regulation. The proposed work aims at characterizing the impact of CADASIL on this pathway and further develop the PIP2 treatment to improve cerebral blood flow in CADASIL mouse model.