# The Role of Red Blood Cell in Stroke-Related Hyperglycemia

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $422,572

## Abstract

Project Summary/Abstract
Acute hyperglycemia following an ischemic stroke is a significant contributor to poor clinical outcome, even
though it is temporary. While intensive insulin treatment can correct hyperglycemia, it does not necessarily
improve patient outcome, suggesting the presence of early hyperglycemic injuries that are resistant to glucose
control. Red blood cells (RBCs), often overlooked in stroke research, are particularly vulnerable to
hyperglycemia due to their exclusive reliance on glucose for energy and limited adaptability to metabolic
disturbances in high glucose condition. Our pilot study has identified abnormal RBC indices in stroke patients
experiencing acute hyperglycemia, which, in turn, were predictive of poor stroke outcome. Further analyses
revealed that acute hyperglycemia may initiate a shift in RBC glucose metabolism from the pentose phosphate
pathway (PPP) towards the hexosamine pathway, potentially resulting in increased oxidative stress within
RBCs. Notably, these RBC changes were unresponsive to glucose normalization, but were able to impair the
function of brain endothelial cells, indicating their novel role in acute hyperglycemic injury in ischemic stroke. In
this multiple PI project, we aim to investigate the role of RBCs in stroke-related hyperglycemia through
translational research and mechanistic studies. We will characterize acute hyperglycemia-related RBC
alterations in clinical stroke patients, with specific focus on RBC glucose metabolism and the consequent
oxidative stress (Aim 1). We will then delve deeper into the mechanisms of RBC alterations in in vitro
hyperglycemic models and assess their impact on brain endothelial functions (Aim 2). Finally, we will validate
our findings in a well-established acute hyperglycemic stroke mouse model and explore the potential of
modifying RBCs to mitigate brain injury and improve stroke outcome in the context of acute hyperglycemia
(Aim 3). Successful completion of this project will yield a comprehensive understanding of the effects of acute
hyperglycemia on RBCs and their consequences on vascular function, ultimately translating into enhanced
clinical care and patient will-being.

## Key facts

- **NIH application ID:** 10980717
- **Project number:** 1R01NS134819-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Wenjun Deng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $422,572
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980717

## Citation

> US National Institutes of Health, RePORTER application 10980717, The Role of Red Blood Cell in Stroke-Related Hyperglycemia (1R01NS134819-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10980717. Licensed CC0.

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