# Neuroprotective role of OGR1 in brain ischemia

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 2020 · $357,142

## Abstract

PROJECT ABSTRACT
Brain acidification occurs in excitotoxicity, following disrupted metabolism, and in multiple diseases including
ischemia, multiple sclerosis, and traumatic brain injury. Given the prevalence of acidosis in disease,
determining molecular mechanisms underlying acid signaling will have broad translational value. It has been
known for decades that acidosis is one key contributing factor to neuronal injury. Paradoxically, a relatively
mild acidosis can be protective. In recent years, a lot of progress has been made on understanding how
acidosis leads to neuronal injury. This is largely due to the discovery of acid-sensing ion channels (ASICs),
which are a family of proton gated cation channels. A series of data, including ours, show that ASICs are the
major postsynaptic proton receptor in brain neurons, and one key mediator of acidosis-induced neuronal injury.
These data on ASICs have greatly advanced our knowledge of acid signaling. However, ASICs do not appear
to explain the protective effect of acidosis. In our preliminary studies, we found that ovarian cancer G protein
coupled receptor 1 (OGR1), a proton-sensitive G protein coupled receptor (GPCR), is widely expressed in the
brain. In addition, OGR1 mediates acid-induced signaling in hippocampal slices. Our data further suggest that
OGR1 mediates a protective pathway in acidotic and ischemic conditions. Here, we will use middle cerebral
artery occlusion, a widely used rodent model for studying ischemia-induced brain injury, and determine
whether OGR1 activation leads to neuroprotection following ischemia. To better understand the mechanism,
we will use in vitro cell culture and slice models to determine downstream signaling that mediates the effect of
OGR1. Results obtained from the proposed study will uncover novel protective mechanisms mediating
extracellular acid signaling, and provide potential molecular targets for the design of novel therapeutic
approaches to alleviate ischemia-induced brain injury.

## Key facts

- **NIH application ID:** 9989656
- **Project number:** 5R01NS102495-04
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Xiangming Zha
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,142
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989656

## Citation

> US National Institutes of Health, RePORTER application 9989656, Neuroprotective role of OGR1 in brain ischemia (5R01NS102495-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989656. Licensed CC0.

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