# Molecular analysis of the blood-nerve barrier in health and diabetes

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $437,250

## Abstract

PROJECT SUMMARY
 In most organs, the vasculature is permeable to many blood-borne molecules and cells, but the vessels of
the nervous system tightly regulate the movement of ions, molecules and cells between the blood and the
nervous tissue. In this way, the vasculature of the nervous system rigorously controls the neural environment to
allow for proper neuronal function, and protect the neural tissue from toxins and pathogens. The blood nerve
barrier (BNB) is the set of vascular characteristics that describes this strict regulation in the peripheral nervous
system (PNS) and is analogous in function to the blood brain barrier (BBB) in the central nervous system (CNS).
Dysfunction of either of these barrier properties has been associated with various pathologies including diabetic
peripheral neuropathy in the PNS and multiple sclerosis in the CNS. Researchers have made great strides in
answering many fundamental questions about BBB biology, especially by leveraging the use of RNA sequencing
to identify genes of importance. In contrast, little is known about the cellular and molecular mechanisms
responsible for BNB function in health and dysfunction in disease. Although the differences in cell types between
the CNS and PNS are well known, no one has performed an in-depth molecular comparison of the BBB and
BNB. Given the clinical relevance of BBB and BNB dysfunction in disease, a thorough comparison of both would
be valuable to advance novel therapeutics for both PNS and CNS diseases, alike. As such, the principal goal
of this proposal is to leverage the use of single cell RNA sequencing technology to compare the gene
expression of the key cell types that form the BNB and BNB under physiological conditions, and
characterize changes in the gene expression of the BNB during diabetic peripheral neuropathy. To
accomplish this, we will first perform single cell RNA sequencing comparing adult mouse sciatic and optic nerves
since these are analogous regions from the PNS and CNS and will have BNB and BBB vasculature, respectively.
We will then perform single cell RNA sequencing on sciatic nerves from diabetic mice at early, mid, and late-
stages of the disease, comparing them with healthy controls. Overall, this proposal will provide transcriptomic
information on the differences between the BNB and BBB in health and BNB dysfunction in a diabetic model,
providing a framework for a more complete understanding of the BNB in an aim to develop novel therapeutic
strategies.

## Key facts

- **NIH application ID:** 11057426
- **Project number:** 1R21NS137238-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Richard Daneman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $437,250
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11057426

## Citation

> US National Institutes of Health, RePORTER application 11057426, Molecular analysis of the blood-nerve barrier in health and diabetes (1R21NS137238-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11057426. Licensed CC0.

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