# Vascular Pannexin 1 in Ischemic Stroke

> **NIH NIH R00** · TUFTS MEDICAL CENTER · 2021 · $249,000

## Abstract

|| PROJECT SUMMARY/ABSTRACT
Ischemic stroke is a significant disease that can lead to neurological deficits or death; however, only one
pharmacological intervention drug is available and it predominately aims to eliminate the physical occlusion
within the blood vessel. To explore potential therapeutic targets to improve recovery following an ischemic
stroke, we began examining the role of Panx1 channels, which activate downstream purinergic receptors,
within the cerebral vasculature. I have recently shown that deletion of endothelial Panx1 profoundly improves
post-cerebral ischemia/reperfusion infarct volume. However, endothelial Panx1 could significant contribute to
both arterial and venous endothelial functions. In this application, we demonstrate that arterial myogenic tone
development (arterial), and inflammation of leukocytes following an ischemic stroke (venous), are significantly
decreased in mice lacking endothelial Panx1. This application tests the hypothesis that endothelial Panx1
contributes to the development of ischemic stroke injury through both regulation of cerebral arterial myogenic
tone and regulation of leukocyte adhesion and emigration in cerebral venous endothelial cells. Our preliminary
data suggest that Panx1 activation during myogenic tone development is regulated through interaction with b3
integrins. Whereas, in cerebral veins, I find leukocyte adhesion in cerebral venules following an ischemic
stroke is regulated through Panx1 channel function. These studies will provide insight into the differential roles
and regulation of Panx1 within arterial and venous cerebral endothelial cells, their contribution to the etiology of
ischemic stroke injury, and lay the foundation for future identification of therapeutic interventions for ischemic
stroke patients.
During the mentored phase of this application, I will develop novel transgenic mice to evaluate the
overexpression of endothelial Panx1 and obtain necessary skills to evaluate the functional consequence of
Panx1-b3 interaction and image cerebral inflammation following an ischemic stroke using in vivo intravital
microscopy techniques. I will continue my professional and scientific development in preparation for the
independent phase with continuous guidance from my mentoring committee. During the independent phase, I
will develop a novel transgenic mouse that will delete or overexpress Panx1 specifically within arterial
endothelial cells and determine the role of arterial verse venous endothelial Panx1 during an ischemic stroke.
In addition, I will establish the downstream purinergic signaling involved in Panx1-dependent leukocyte
adhesion, by in vivo imaging of cerebral venules, and emigration, using flow cytometry, and its impact of
determining the severity of an ischemic stroke. This project will foster my continued scientific and professional
training and facilitate my establishing an independent research program in academia.

## Key facts

- **NIH application ID:** 10136704
- **Project number:** 5R00HL143165-04
- **Recipient organization:** TUFTS MEDICAL CENTER
- **Principal Investigator:** Miranda E Good
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136704

## Citation

> US National Institutes of Health, RePORTER application 10136704, Vascular Pannexin 1 in Ischemic Stroke (5R00HL143165-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10136704. Licensed CC0.

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