# Comparative Gene Expression in Human vs Rodent Stroke Models

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $313,442

## Abstract

Project Summary:
The failure of many clinical trials in ischemic stroke has led to increasing debate about whether mouse and rat
models are valid. We propose that the key for translational stroke research is not whether rodent models can
completely predict ALL treatments for human stroke, but how to correctly use cell and animal models for drug
development, depending on the mechanisms being targeted. It is likely that when mouse and rat models are
compared to human stroke, some targets and mechanisms are the same and some are different. However,
there are no systematic studies to assess similarities and differences between mouse and rat cells and models
vs human stroke patients. This is the critical gap in translation that we seek to fill. In this project, we will map
gene expression after oxygen-glucose deprivation or cerebral ischemia in neurons, astrocytes and microglia
from mouse, rats and humans, and build a comparative database of network and pathway responses in all
three species.
In Aim 1, we will detect gene expression in primary neurons, astrocytes and microglia from mouse, rat or
human under baseline condition and after oxygen-glucose deprivation by gene array, and assess pathways
with standard Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis.
Upregulation or downregulation of pathways will be assessed via z-scores based on MetaBase and Ingenuity
databases. In Aim 2, we will determine gene response in neurons, astrocytes and microglia in peri-ischemic
cortex after focal cerebral ischemia in young vs aged as well as normotensive vs hypertensive mouse and rat
models for comparison with six validated human stroke patients. mRNA levels and gene pathway responses
will again be assessed with gene array and KEGG/GO analysis. Upregulation or downregulation of pathways
will be assessed via z-scores based on MetaBase and Ingenuity databases.
This project will produce a relational and interactive database of neuronal, astrocytic and microglial gene
networks and pathways that respond to oxygen-glucose deprivation in vitro and ischemia in vivo. This
comparative database will allow us to (a) compare rodents vs human stroke, (b) compare primary cell culture
vs in vivo models, and (c) compare young vs aged animals, and (d) compare normotensive vs hypertensive
animals. Ultimately, this relational and interactive database should allow users to interrogate potential
mechanisms and targets for translation in cell and rodent stroke models.

## Key facts

- **NIH application ID:** 9959514
- **Project number:** 5R01NS094392-05
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Changhong Xing
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,442
- **Award type:** 5
- **Project period:** 2018-07-27 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959514

## Citation

> US National Institutes of Health, RePORTER application 9959514, Comparative Gene Expression in Human vs Rodent Stroke Models (5R01NS094392-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9959514. Licensed CC0.

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