# Cerebral endothelial cells derived exosomes as a therapy for cognitive impairment in aged diabetic rats

> **NIH NIH R01** · HENRY FORD HEALTH SYSTEM · 2021 · $358,623

## Abstract

Abstract:
 Diabetes mellitus (DM) induces cerebral vascular dysfunction and impairs the hippocampal neurogenesis,
resulting in cognitive decline. Cerebral angiogenesis couples with neurogenesis. Molecules that mediate the
interaction between cerebral endothelial cells and neural stem cells in particular in DM have not been fully
investigated. Cerebral endothelial cells constitutively release exosomes, which mediate intercellular
communication. Our preliminary data demonstrated that exosomes derived from dysfunctional cerebral
endothelial cells of DM rats communicate with neural stem cells and inhibit neurogenesis. Importantly,
administration of exosomes isolated from cerebral endothelial cells (CE-exo) of healthy adult brain to DM rats
robustly improved cognitive function and minimized DM-induced cerebral endothelial cell dysfunction and DM-
impaired hippocampal neurogenesis. In this application, we therefore, propose to develop cerebral endothelial
exosomes as a mechanism-based therapy for DM-induced cognitive decline in the aged rats. There are three
Aims. Aim 1 tests the hypothesis that CE-exo treatment reduces cognitive deficits in the DM rat. Aim 2 tests
the hypothesis that CE-exo treatment improves cerebral vascular patency and integrity, and promotes
neurogenesis in the aged-DM rat. Aim 3 tests the hypothesis that engineered exosomes carrying elevated
selective miRNAs have enhanced effects on cerebral vascular function and neurogenesis as well as cognitive
function. These studies will provide preclinical evidence for developing CE-exo as an innovative treatment for
DM-induced cognitive dysfunction.

## Key facts

- **NIH application ID:** 10211376
- **Project number:** 1R01AG068072-01A1
- **Recipient organization:** HENRY FORD HEALTH SYSTEM
- **Principal Investigator:** LI ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $358,623
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211376

## Citation

> US National Institutes of Health, RePORTER application 10211376, Cerebral endothelial cells derived exosomes as a therapy for cognitive impairment in aged diabetic rats (1R01AG068072-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10211376. Licensed CC0.

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