# Enhanced Mitochondrial Function to Increase Effectiveness of Post-Stroke Rehabilitation

> **NIH VA I01** · SOUTHERN ARIZONA VA HEALTH CARE SYSTEM · 2023 · —

## Abstract

The long-term goal of this project is to identify new therapeutics that are effective after a stroke
has occurred to stimulate recovery of cognitive and motor function. Stroke-induced dysfunction
is the result of neuronal injury and death, and mitochondrial dysfunction is implicated in these
processes. Currently, drug therapy to treat stroke is limited to TPA, which must be administered
within 6h of a stroke. This window is too short and TPA has significant side effects. In addition,
therapies are needed that not only treat the initial phase of stroke induced cellular dysfunction
but also will enhance the chronic phase recovery of function and produce enduring benefits.
Our preliminary studies revealed that mitochondrial dysfunction occurred in ipsilesion cortex and
striatum following experimental focal sensorimotor cortex (SMC) ischemic stroke and persisted
over the first week. Consequently, we propose that therapeutics that increase mitochondrial
biogenesis (MB) will promote recovery from stroke in both adult and aged mice. As part of our
drug discovery program to identify chemicals that induce MB, formoterol, a specific long-acting
β2-adrenergic receptor (β2AR) agonist, was identified. Formoterol is an FDA-approved drug to
treat asthma. Preliminary studies demonstrated that formoterol induced MB in naïve animals.
Additionally, our preliminary studies revealed that formoterol administered 24h after stroke
improved forelimb motor recovery after six days. Finally, preliminary studies demonstrated that
daily formoterol administration, beginning 24h after experimental stroke and continuing daily
during forelimb rehabilitative treatment (RT) for 15 days, improved forelimb motor recovery
compared to vehicle administration with or without RT. More specifically, we hypothesize that
stimulating MB with formoterol after stroke will 1) improve mitochondrial function early after
stroke, thus decreasing motor impairments and 2) during RT will improve the efficacy of RT by
supporting experience-dependent neuronal remodeling and repair in adult and aged mice. We
hypothesize that the combination of formoterol and RT will be most beneficial in aged stroke
animals.
Specific Aim 1: Elucidate the optimal formoterol dose to induce MB, restore MF, and
improve behavioral outcomes after experimental stroke in adult and aged mice.
Specific Aim 2: Determine the efficacy of formoterol and forelimb rehabilitative training
(RT) following experimental stroke to enhance MF, MB, structural plasticity and
behavioral outcomes in adult mice.
Specific Aim 3. Determine the efficacy of formoterol and forelimb rehabilitative training
(RT) following experimental stroke to enhance MF, MB, structural plasticity and
behavioral outcomes in aged mice.
Successful completion of these studies will provide strong evidence for the dose, timing and
persistence of formoterol-induced recovery from stroke and a possible mechanism underlying
these findings, providing new targets for rehabilitative ...

## Key facts

- **NIH application ID:** 10490270
- **Project number:** 5I01RX003224-04
- **Recipient organization:** SOUTHERN ARIZONA VA HEALTH CARE SYSTEM
- **Principal Investigator:** Rick G Schnellmann
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490270

## Citation

> US National Institutes of Health, RePORTER application 10490270, Enhanced Mitochondrial Function to Increase Effectiveness of Post-Stroke Rehabilitation (5I01RX003224-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10490270. Licensed CC0.

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