# Monitoring rapid guanosine signaling during ischemia

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2022 · $375,982

## Abstract

PROJECT SUMMARY
Measuring dynamic guanosine signaling at the site of focal ischemia over time remains challenging to probe with
existing technology yet knowledge of the dynamics, regulatory mechanisms, and function of local guanosine
fluctuations during ischemia would positively impact our understanding of the brain’s immediate local
neuroprotective response. Guanosine is a nucleoside purine which has been postulated to play a potent restorative
role after ischemic injury; however, to date, the mechanism and dynamics of guanosine action in the brain remains
unresolved. Additionally, knowledge of the extent to which guanosine signaling changes as a function of ischemia
duration and severity would provide critical insight into guanosine’s role as a neuroprotector. We propose to solve
a significant gap in the understanding of guanosine signaling dynamics during focal ischemia by developing a
microfluidic platform to initiate sustained local oxygen-glucose deprivation in a sub-region of a brain slice and using
fast-scan cyclic voltammetry (FSCV) recording of guanosine with millisecond-to-second temporal resolution to
provide critical insight into the mechanisms of guanosine regulation. Measuring local guanosine dynamics at the
site of injury with significantly improved spatiotemporal resolution will provide critical information of the brain’s
immediate local damage response. This proposal fits within our long-term goal to develop analytical tools to detect
and understand dynamic neurochemical-regulated inflammation in the brain during injury. The rationale for this
proposal is that these tools will provide knowledge of the dynamics, mechanism, and function of rapid guanosine
signaling in the brain during ischemia for the first time which could further inform the development of guanosine-
targeted therapies for neurological injury. The proposal will be completed by the following three specific aims: (1)
Develop microfluidic platforms for delivery of spatiotemporally controlled and sustained focal ischemia to brain
slices, (2) Characterize the mechanism of rapid guanosine release and clearance in the hippocampus as a function
of ischemia severity and location, and (3) Characterize the impact of rapid guanosine signaling on local adenosine
changes during focal ischemia. We will pursue these aims with an innovative approach by using novel microfluidic
platforms for time-controlled delivery of ischemia to brain slices coupled to rapid electrochemical recording of
guanosine signaling with FSCV for the first time. This work is significant because these studies will enable
extraordinary mechanistic insight into the brain’s immediate response to ischemia over varying ischemia durations
and severities which will directly impact future therapeutic strategies for brain injury. The tools are translatable to
any biological system to study local tissue responses. The expected outcome is a new platform to investigate rapid
endogenous guanosine signaling in the brain...

## Key facts

- **NIH application ID:** 10331885
- **Project number:** 5R01NS121426-02
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Ashley E Ross
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,982
- **Award type:** 5
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331885

## Citation

> US National Institutes of Health, RePORTER application 10331885, Monitoring rapid guanosine signaling during ischemia (5R01NS121426-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10331885. Licensed CC0.

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