# The glial mechanism for electrical brain stimulation

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2021 · $748,560

## Abstract

PROJECT SUMMARY/ABSTRACT:
Electrical brain stimulation (EBS) is a FDA-approved neuromodulation therapy applied to several
neurological disorders. However, the molecular basis of its efficacy remains unclear. Here we
propose investigation of a glial mechanism for EBS mediated by astrocytes-derived extracellular
vesicles (EVs). We recently discovered from both in vitro and in vivo experiments that electrical
stimulation affects the release of EVs from astrocytes. In this proposal we will address two questions:
1) what is the molecular mechanism of electrical stimulation induced EVs release; 2) what is the
biological function of the EVs released under electrical stimulations. Our exploratory research plan
includes the following three steps: First - molecular characterization of astrocytic EVs (Aim1). In this
aim we start from primary cultured astrocytes and systematically evaluate the effect of electrical
stimulation parameters on EV cargos; Second - molecular mechanisms of how stimulation affects
astrocytic EVs (Aim 2). In this aim we apply a high-resolution imaging technique to primary cultured
astrocytes and focus on the trafficking of intracellular vesicles, including vesicle fusion to or budding
off the plasma membrane. Third - functional characterizations of astrocytic EVs (Aim 3). In this aim,
we will subject purified EVs collected in step 1 to both in vitro and in vivo functional testing. Focusing
on neuronal activities as readout, we will first examine EV functions on primary cultured neurons; then
we use in vivo animal models combined with 2-photon microscope technology to examine how EVs
affect neuronal activities in both short- and long-term periods, and also how EVs affect animal
behavior. In summary, our findings will help guide optimization of stimulation with next-generation
EBS devices, with the ultimate goal of enhancing efficacy and treatments for patients with
neurological disorders.

## Key facts

- **NIH application ID:** 10218282
- **Project number:** 5R01NS112144-03
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Hai-Long Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $748,560
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10218282

## Citation

> US National Institutes of Health, RePORTER application 10218282, The glial mechanism for electrical brain stimulation (5R01NS112144-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10218282. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*