# The Effect of Blood Flow Changes in Brain Microvasculature on Pericyte-Endothelial Cell Interaction

> **NIH NIH F31** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $43,531

## Abstract

PROJECT SUMMARY
Stroke is one of the most common causes of death and disability in the United States and worldwide. The
vascular system is meticulously regulated throughout life to adapt to changes in metabolic demand and blood
flow under widely variable conditions. Many ischemic stroke patients however fail to fully recover following an
acute attack. This impaired recovery is related in part to the limited return of perfusion within the brain
microcirculation, even after restoring the patency of occluded vessels – a scenario referred to as the “no-reflow”
phenomenon. Blood circulating within the vascular system exerts different types of forces on the surrounding
vessels. These forces are sensed and interpreted by the vascular cells to guide their development during
embryogenesis and regulate remodeling during postnatal and adult life. It has been also suggested in recent
years that there are signals downstream of mechanical changes that are exchanged between vascular cells.
Specifically, pericytes and endothelial cells integrate these cues to dynamically regulate blood vessel physiology,
capillary permeability, and changes in microvascular tone in health and in disease. Despite recent advances in
our knowledge of flow-mediated biomechanical inputs, the underlying molecular processes and their link to
hemodynamic forces in vivo are still emerging, in part due to limitations in the tools and models to measure these
forces. To help fill this gap in knowledge, the proposed study aims to investigate the impact of abrupt changes
in blood flow on two components of the blood-brain barrier -- pericytes and endothelial cells -- and their interaction
in mature brain vessels under static conditions following the loss of flow. We will utilize both ex vivo and in vivo
models to establish the mechanistic interactions underlying how pericytes and endothelial cells process,
interpret, and organize various mechanical signals. Additionally, we will look at corresponding changes in the
surrounding extracellular matrix that might accompany this cellular interplay, specifically interactions between
endothelial cell integrin α5 and pericyte-derived vitronectin within the capillary wall. Our preliminary data suggests
a two-phase response over time following an acute shift towards static conditions. We propose that an early
stage marked by a rapid inflammatory response, involving elevated interleukin-1beta expression, is overlaid by
a hypoxia-driven response in a subsequent phase, both contributing to cerebrovascular instability and an
increased risk for hemorrhagic conversion of ischemic stroke patients after re-establishing cerebral blood flow.
Identifying the key mechanistic determinants responsible for blood vessel destabilization in the brain during the
hyper-acute phase of stroke will provide targetable signals that could be clinically significant in advancing stroke
therapies.

## Key facts

- **NIH application ID:** 10841393
- **Project number:** 5F31HL168946-02
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Hanaa Abdelazim
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $43,531
- **Award type:** 5
- **Project period:** 2023-04-10 → 2025-06-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841393

## Citation

> US National Institutes of Health, RePORTER application 10841393, The Effect of Blood Flow Changes in Brain Microvasculature on Pericyte-Endothelial Cell Interaction (5F31HL168946-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10841393. Licensed CC0.

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