# Molecular probes to image and target the neurovascular unit in health and disease

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $606,191

## Abstract

ABSTRACT
Endothelial cells (ECs), astrocytes and pericytes are integral components of the neurovascular unit (NVU) and
play critical roles in blood brain barrier (BBB) formation and maintenance. These cells express uptake and
efflux membrane transporters that regulate CNS penetration of molecules, therapeutic drugs and toxins. The
function of the BBB and transporters is likely disrupted in many neurological disorders. Thus, development of
tools to study NVU cells and their properties of BBB selective transport in vivo is a key priority in translational
neuroscience research. We have discovered a unique set of small molecules that can be selectively
transported into the cytoplasm of either ECs, pericytes or astrocytes with exquisite affinity and specificity. We
have evidence that these molecules enter cells through membrane transporters, selectively expressed in each
cell type. We hypothesize that these molecules could be adapted as probes for intravital animal and human
imaging and also for cell-specific delivery of drugs. In this proposal, we aim to identify the precise mechanisms
of probe membrane transport in vivo; establish the feasibility of using these molecules as cell-specific drug
carriers or as radiopharmaceuticals for human imaging with positron emission tomography (PET) and finally
test their in vivo properties in models of Alzheimer's disease and stroke. This project will improve our
understanding of molecular transport mechanisms across the BBB and may transform the ability to selectively
image and pharmacologically modulate cells of the NVU in health and disease.

## Key facts

- **NIH application ID:** 10545711
- **Project number:** 5R01NS115544-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jaime Grutzendler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $606,191
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10545711

## Citation

> US National Institutes of Health, RePORTER application 10545711, Molecular probes to image and target the neurovascular unit in health and disease (5R01NS115544-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10545711. Licensed CC0.

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