# Role of Patrolling Monocytes in Cerebral Vascular Repair during HIV/Substance Abuse

> **NIH NIH K01** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $149,899

## Abstract

Abstract (30 lines or less)
HIV-associated neurocognitive disorders (HAND) remain a concern in the US and worldwide for the nearly 40
million people living with HIV. One of the hallmark features of HAND pathogenesis is the infiltration of immune
cells and viral replication in the brain. This process occurs in part due to a loss of blood-brain barrier (BBB)
integrity, which results in hyperpermeability and increased immune cell extravasation. Additionally, it is well
established that drugs of abuse can exacerbate HAND by augmenting blood-brain barrier (BBB) dysfunction
and neuroinflammation. The mechanisms that govern BBB resilience, or lack thereof, and recovery during
HIV/substance abuse remain understudied. This proposal is based on the central premise that understanding
these mechanisms could identify means to speed BBB recovery, attenuate immune cell infiltration and
ultimately slow the progression of HAND. We are focused on a subclass of immune cells, non-classical
monocytes or patrolling monocytes, that have been identified for their unique functions in vascular
maintenance and homeostasis. Patrolling monocytes have been shown to survey the luminal endothelial
surface, scavenge debris and initiate vascular repair. These processes are clearly positive effects that aid in
the preservation and recovery of the vasculature. However, the functions of these specialized cells have not
been studied in the context of substance abuse or HIV. We will test the central hypothesis that cocaine impairs
patrolling monocyte function and repair of the BBB. Additionally, we will also investigate the innovative concept
that the cerebral vascular endothelium communicates the need for vascular repair through extracellular
vesicles. We propose a multilateral approach that utilizes in vivo models, advanced in vitro microfluidic
modeling of the BBB, and analysis of clinical samples to understand the role and function of patrolling
monocytes in the context of HIV/substance abuse. Importantly, our use of advanced in vitro microfluidic
modeling of the BBB with primary human cells presents the opportunity to study endothelial-immune
interactions in a way that more closely mimics the human in vivo environment. Overall, the studies
encompassed in this proposal will advance current knowledge regarding patrolling monocyte function, cerebral
endothelial-immune interactions, and establish a novel mechanism by which drugs of abuse contributes to
HAND.

## Key facts

- **NIH application ID:** 10080722
- **Project number:** 5K01DA046308-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Allison Michelle Andrews
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $149,899
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080722

## Citation

> US National Institutes of Health, RePORTER application 10080722, Role of Patrolling Monocytes in Cerebral Vascular Repair during HIV/Substance Abuse (5K01DA046308-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10080722. Licensed CC0.

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