# Novel therpeautic interventions to treat ischemic stroke

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $322,637

## Abstract

Project Summary
Stroke results in immense health and economic burden. Current strategies to improve stroke outcome is
fibrinolysis of the clot with tissue plasminogen activator and mechanical thrombectomy, which involves
reperfusion of the ischemic region. However, accumulating evidence suggests that cerebral reperfusion is
often accompanied by oxidative stress, thrombosis, and vascular inflammation, which exacerbates neuronal
death in the ischemic penumbra. There is currently no effective intervention available to protect the brain
damage following reperfusion therapy. Clinical studies have shown a positive correlation between the
massive influx of neutrophils and severity of injury following reperfusion. Integrin alpha9beta1 is highly
expressed on neutrophils (relative to monocytes), upregulated upon activation and transmigration, and is
known to stabilize neutrophil adhesion to activated endothelium in synergy with alpha2beta1 integrin. The
mechanistic role of alpha9beta1 in stroke outcome is not explored yet. Utilizing novel mutant strains, in pilot
studies, we found that alpha9beta1 exacerbates stroke outcome by modulating thrombosis and vascular
inflammation. Following updated Stroke Therapy Academic Industry Roundtable (STAIR) pre-clinical
guidelines and compelling pilot data, we propose to test the innovative hypothesis that integrin alpha9beta1
contributes to ischemic stroke exacerbation in stroke models with comorbidities and therapeutic targeting
alpha9beta1 will improve stroke outcome by limiting thrombosis and inflammation. To accomplish this, we
will utilize complementary genetic and pharmacological approaches, state-of-the-art intravital microscopy,
magnetic resonance imaging, laser speckle imaging and follow current STAIR/RIGOR guidelines. Aging and
biological sex are key determinants that influence stroke outcome. We will determine whether targeting
alpha9beta1 will improve stroke outcome in the context of biological sex and aging so that the observed
effect is generalizable to the broader context. This project may have significant clinical implications since
understanding the mechanisms by which neutrophils contribute to reperfusion injury in stroke models with
comorbidities may provide new therapeutic interventions to treat ischemic stroke.

## Key facts

- **NIH application ID:** 10054977
- **Project number:** 5R01NS109910-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Anil Kumar Chauhan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $322,637
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054977

## Citation

> US National Institutes of Health, RePORTER application 10054977, Novel therpeautic interventions to treat ischemic stroke (5R01NS109910-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10054977. Licensed CC0.

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