# Rewiring the Injured Brain with GABA Progenitors

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $433,546

## Abstract

Abstract
Transplantation of neural progenitor cells has extraordinary potential for the treatment of many nervous system
disorders. Several recent studies have shown that progenitor cells derived from the embryonic mouse medial
ganglionic eminence (MGE) retain a unique ability to migrate and differentiate into GABAergic interneurons
following transplantation into the juvenile or adult rodent brain. We recently demonstrated that these cells are
effective in correcting memory impairments and preventing spontaneous seizures in a mouse model of
traumatic brain injury. However, it is not known whether similar therapeutic effects can be achieved with
clinically-relevant cell sources, such as human pluripotent stem cells. Here, we propose studies to evaluate the
effect of human-derived interneurons in a pre-clinical model of traumatic brain injury. Our approach involves
transplantation of human interneuron progenitors into a widely-used rodent model of closed-head injury at
different stages following injury followed by in vitro patch-clamp recordings, immunofluorescence techniques
and neural circuit mapping to evaluate the synaptic integration of grafted neurons. A battery of behavioral
assays and video-EEG monitoring will also be applied. Two specific aims are proposed: (i) determine how
human-derived GABA progenitors integrate into brain injured hippocampus, and (ii) test the therapeutic
efficacy of human GABA neurons in a mouse model of traumatic brain injury. If successful, our results will help
move these exciting technologies closer to the clinic by establishing relatively direct proof of concept for human
interneuron transplantation to treat traumatic brain injury.

## Key facts

- **NIH application ID:** 10367991
- **Project number:** 5R01NS096012-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Robert F Hunt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $433,546
- **Award type:** 5
- **Project period:** 2016-02-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367991

## Citation

> US National Institutes of Health, RePORTER application 10367991, Rewiring the Injured Brain with GABA Progenitors (5R01NS096012-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10367991. Licensed CC0.

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