# Astrocytic LRP-1 Modulates Blood-Brain Barrier Function

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Objective:
The main goal of this application is to study the mechanism whereby the low density
lipoprotein receptor-related protein 1 (LRP1) modulates the permeability of the BBB
under physiological conditions and after an ischemic stroke.
Methods
In Aim I we will test the hypothesis that under non-ischemic conditions astrocytic LRP1
preserves the integrity of the basement membrane-astrocyte (BM-A) interface by
promoting the recruitment of integrins to the membrane of perivascular astrocytic end-
feet processes and their binding to its ligands in the basement membrane (BM). In Aim II
we propose that this function is lost under ischemic conditions when the cleavage of the
extracellular domain of LRP1 from perivascular astrocytes activates a cell-signaling
pathway that increases the permeability of the blood-brain barrier (BBB). In Aim III we
will study in an animal model of ischemic stroke whether inhibition of LRP1 cleavage
from perivascular astrocytes with the receptor-associated protein (RAP) prevents the
harmful effects of endogenous tPA and/or rtPA on the permeability of the BBB.
Research Plan
In the first Aim of this application we will use astrocytic cell cultures and a cell adhesion
assay. In the second Aim we will use astrocytic cultures, an in vitro model of the blood-
brain barrier, real-time PCR, confocal microscopy and co-immunoprecipitation assays. In
the third Aim we will use a nanocarrier that we engineered to selectively deliver its
content to the BBB in the ischemic tissue and an animal model of cerebral ischemia.

## Key facts

- **NIH application ID:** 9898289
- **Project number:** 5I01BX003441-04
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Manuel Salvador Yepes
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898289

## Citation

> US National Institutes of Health, RePORTER application 9898289, Astrocytic LRP-1 Modulates Blood-Brain Barrier Function (5I01BX003441-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9898289. Licensed CC0.

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