# Understanding the relationships between FUS-BBB opening, neuroinflammation and the neurovascular response

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $218,878

## Abstract

Project Summary:
The blood-brain barrier (BBB) is a critical protective structure that tightly controls which biologics are able to pass
from the blood stream into the brain parenchyma, excluding toxins but also preventing the delivery of almost all
neurotherapeutics. Focused ultrasound (FUS) is an emerging technology that allows the possibility of non-
invasive and controlled opening of the BBB for delivery of therapeutics that would not otherwise reach the brain.
Using conservative protocols, FUS-BBB opening procedures are being done today in clinical trials, safely and
successfully, for treatment of several neurological diseases. Expansion to a wider range of clinical applications
will require treatment parameters to be pushed into a regime where the safety concerns related to secondary
effects of BBB disruption are not fully understood. These concerns include the initiation of inflammatory and
immune responses and, recently demonstrated by our group, alteration of cerebral blood flow regulation. In this
project we aim to understand the relationships between FUS-BBB opening, neuroinflammation, and alteration of
cerebral blood flow regulation so that the field of FUS-BBB opening can be moved forward safely into new
applications. We will use state of the art optical imaging techniques to directly measure the neuronal, astrocytic,
and blood flow components of the neurovascular response following FUS-BBB opening. Markers of the
inflammatory response will be assessed in brain samples collected immediately after imaging. The data will be
acquired over a range of intensities, time points, and drug effects in order to elucidate the key mechanisms that
link FUS-BBB opening, neuroinflammation, and the suppression of the neurovascular response. In Aim 1 we will
focus on the role of neuronal and astrocytic activity following FUS-BBB opening and how changes in their
signaling can affect the blood flow component of the neurovascular response. In Aim 2 we will define the
relationships between markers of acute neuroinflammation and the attenuation of the neurovascular response,
including the effects of an anti-inflammatory drug given at the time of FUS-BBB opening. In Aim 3 we will
investigate the effects of repeated FUS-BBB opening on these fundamental processes, including testing the
hypothesis that pre-conditioning the inflammatory process will allow subsequent BBB openings to be achieved
with a muted response. This project will deliver significant new knowledge regarding the relationship between
FUS-BBB opening, the inflammatory response, and attenuation of the neurovascular response. Gaining this
knowledge is critical for safely driving the field of FUS-BBB opening into new clinical applications.

## Key facts

- **NIH application ID:** 10251997
- **Project number:** 5R21EB030173-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Cleide Angolano
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,878
- **Award type:** 5
- **Project period:** 2020-09-02 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251997

## Citation

> US National Institutes of Health, RePORTER application 10251997, Understanding the relationships between FUS-BBB opening, neuroinflammation and the neurovascular response (5R21EB030173-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10251997. Licensed CC0.

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