# Recombinant FGF21 as a novel approach for treating ischemic stroke in type 2 diabetes

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2020 · $332,500

## Abstract

Project Summary
Diabetic stroke patients have higher mortality and worse neurological outcomes. Emerging clinical and
experimental data suggest that BBB disruption, neuroinflammation, and stroke recovery impairment are
exacerbated in T2D. Hence, the goal of this project is to investigate therapeutic approaches that can target
these specific T2D mechanisms in stroke. Fibroblast Growth Factor-21 (FGF21) is a circulating endocrine
hormone that is primarily expressed in the liver. FGF21 has pleiotropic metabolic actions, but also has tissue
protective and repair roles. Here, we will test the overall hypothesis that exogenous recombinant human
FGF21 (rFGF21) activates FGFR1--klotho complex that may ameliorate T2D-affected mechanisms after
stroke via: (1) activation of PPAR for BBB protection, (2) inhibition of NFB-mediated but activation of PPAR
for neuroinflammation modulation, (3) promotion of AMPK/Nrf2-mediated vascular/white matter remodeling to
boost neurorestoration after stroke.
Aim 1. Investigate rFGF21 effects on blood-brain barrier integrity in T2D stroke mice. We will examine FGF21
specific receptor FGFR1 phosphorylation, PPAR activity, BBB integrity, hemorrhagic transformation,
expression of vascular inflammatory molecules and tight junction proteins, are assessed up to 3 days after
stroke (dMCAO) in db/db T2D mice, and T2D stroke in vitro model of brain endothelial/astrocytes co-cultures.
Aim 2. Investigate rFGF21 effects on neuroinflammation in T2D stroke. We will examine NFB and PPAR
activation, and correlation with microglia/macrophage activation, pro-inflammatory factor expression in peri-
lesion area by RT-PCR, immunohistochemistry, western blots, and flow cytometry after focal dMCAO stroke in
T2D mice, and in primary microglia cultures in vitro. Aim 3. Investigate rFGF21 effects on vascular/white
matter remodeling in T2D stroke. We will examine activation of AMPK and Nrf2, expression of trophic factors in
isolated brain microvascular fragments and brain tissues by western blot analysis, immunohistochemistry, and
mRNA microarray. We will also test biomarkers of vascular and white matter remodeling over time by
immunohistochemistry, RT-PCR and western blots after ischemic stroke of T2D mice, and in vitro models of
primary human brain endothelial cultures and oligodendrocyte cultures.

## Key facts

- **NIH application ID:** 9963406
- **Project number:** 5R01NS099539-06
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** XIAOYING WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $332,500
- **Award type:** 5
- **Project period:** 2019-08-02 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963406

## Citation

> US National Institutes of Health, RePORTER application 9963406, Recombinant FGF21 as a novel approach for treating ischemic stroke in type 2 diabetes (5R01NS099539-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9963406. Licensed CC0.

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