# Neurovascular Interactions: Mechanisms, imaging, therapeutic potential

> **NIH NIH R35** · J. DAVID GLADSTONE INSTITUTES · 2020 · $1,368,800

## Abstract

PROJECT SUMMARY/ABSTRACT
The neurovascular interface fundamentally changes during CNS diseases due to increased blood-brain barrier
permeability and influx of plasma proteins in the CNS parenchyma. Studying neurologic diseases through the
multidisciplinary prism of vascular biology, immunology, and neuroscience could be critical for the identification
of novel mechanisms of disease, discovery of imaging tools and therapeutic treatments for a wide range of
neurologic diseases characterized by BBB disruption. In my laboratory we made unanticipated discoveries on
the functional role of BBB disruption in CNS autoimmunity, glial cell activation, and neurodegeneration. We
identified leakage of blood proteins in the brain and neurotrophin receptor signaling as novel molecular mediators
at the neurovascular interface that regulate glial – neuron cross-talk and the communication between the brain
and the immune system. Furthermore, we developed novel methods for high-resolution two-photon microscopy
of the neurovascular interface in vivo. Our aim is to understand the mechanisms that control the communication
between the brain, immune and vascular systems with the ultimate goal to design novel therapies for neurologic
diseases. In this application we propose a multipronged approach to determine the role of neurovascular
dysfunction in neurodegeneration, CNS repair, and glial cell biology and discover novel genetic regulatory circuits
that control vascular-driven CNS innate immune mediated neurotoxicity. We use an innovative experimental
design consisting of in vivo two-photon, super-resolution and electron microscopy of the neurovascular interface,
electrophysiology, cell biology and signal transduction, new genetic tools and animal models, and genomic and
proteomic approaches. The proposed studies will set the foundation how neurovascular dysfunction regulates
brain functions and the outcomes of this research would be applicable for the understanding of the etiology and
the development of new treatments for several neurologic diseases, such as multiple sclerosis, stroke, spinal
cord and brain injury.

## Key facts

- **NIH application ID:** 10019602
- **Project number:** 5R35NS097976-05
- **Recipient organization:** J. DAVID GLADSTONE INSTITUTES
- **Principal Investigator:** Katerina Akassoglou
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,368,800
- **Award type:** 5
- **Project period:** 2016-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019602

## Citation

> US National Institutes of Health, RePORTER application 10019602, Neurovascular Interactions: Mechanisms, imaging, therapeutic potential (5R35NS097976-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019602. Licensed CC0.

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