# Brain Vascular Signatures in Drug-induced Recurrent Hypoglycemia and Associated Cognitive Dysfunction

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2024 · $433,576

## Abstract

ABSTRACT
Type 2 diabetes mellitus (T2DM) poses a serious global health issue, affecting millions globally, with a
concerning rise in younger age groups. T2DM patients often suffer from hypoglycemia, typically medication-
induced, leading to severe consequences and cognitive impairment. Frequent hypoglycemic episodes can give
rise to 'hypoglycemia unawareness,' escalating the risk of severe hypoglycemia and cognitive decline, including
dementia. Investigating cognitive alterations induced by hypoglycemia in T2DM patients is complex due to the
interplay of vascular responses, brain activity, and cognitive functions. Current functional imaging techniques
can visualize brain vascular parameters but lack compatibility with behavioral assessments, creating a challenge
to correlate brain activity with cognitive functions.
Our research project aims to unravel the intricate connections between vascular responses and cognitive
dysfunction influenced by recurrent hypoglycemia. To achieve this, we will employ a novel head-mounted dual-
modality photoacoustic/ultrasound localization (PAUL) imaging technique. With its exceptional resolution, PAUL
imaging allows us to visualize detailed patterns of brain blood flow and blood oxygenation, providing data on par
with fMRI. We anticipate that this advanced imaging method will enable the visualization of dynamic changes
in brain vascular signatures during cognitive assessments. Through this innovative approach, we expect to gain
valuable insights into the association between hypoglycemia and cognitive impairment.
Our approach involves three distinct aims. First, we plan to investigate the effects of various hypoglycemia
conditions on brain vascular responses in anesthetized rats with T2DM. By inducing diabetes in middle-aged
rats and employing PAUL imaging, we aim to record vascular responses under varying insulin-induced
hypoglycemia levels, frequencies, and recurrent lengths. Second, we will design a lightweight head-mounted
probe for high-quality PAUL imaging of brain vascular responses in freely moving rats, reducing stress during
cognitive assessments. Lastly, we aim to scrutinize the brain vascular signatures and cognitive functions in rats
with recurrent hypoglycemia. This will involve assessing cognitive behaviors while simultaneously imaging brain
blood flow and oxygenation, alongside monitoring glucose levels.

## Key facts

- **NIH application ID:** 10850293
- **Project number:** 1R01DK138939-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** YUN-SHENG CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $433,576
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10850293

## Citation

> US National Institutes of Health, RePORTER application 10850293, Brain Vascular Signatures in Drug-induced Recurrent Hypoglycemia and Associated Cognitive Dysfunction (1R01DK138939-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10850293. Licensed CC0.

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