# Exosome therapy for acute stroke with large artery occlusion

> **NIH NIH R01** · HENRY FORD HEALTH SYSTEM · 2022 · $395,252

## Abstract

Abstract:
Large cerebral vessel occlusion is the most disabling and life-threatening form of ischemic stroke.
Human stroke primarily occurs in late middle age and beyond. Approximately two thirds eligible patients
treated with tPA experience incomplete reperfusion. Thrombectomy is now also a standard of care for
treatment of acute stroke with large vessel occlusion. However, recanalization of the occluded large vessels
by thrombectomy only leads to ~71% of patients achieving improved tissue reperfusion, often incomplete. In
addition, due to unfavorably large ischemic cores, many patients with large artery occlusion are not eligible to
receive tPA or thrombectomy. Patients with reperfusion of the ischemic tissue are closely associated with
good clinical outcome. Thus, there is a compelling need to develop therapies in combination with tPA and
thrombectomy to enhance cerebral perfusion and thereby augment the therapeutic efficacy of tPA and
thrombectomy monotherapies. Also, therapies to block ischemic core expansion will increase numbers of
patients who would be eligible to receive tPA and thrombectomy. Using rat models of embolic middle cerebral
artery occlusion (eMCAO) and transient MCAO (tMCAO, ischemia/reperfusion), we found that exosomes
derived from cerebral endothelial cells (CEC- exos) in combination with tPA after eMCAO or CEC-exos
given upon reperfusion after tMCAO substantially increased recanalization and downstream cerebral blood
flow (CBF), and reduced blood brain barrier (BBB) leakage and infarction compared to tPA or tMCAO alone.
Exosomes are nano-vesicles that contain lipids, proteins, and RNAs including microRNAs (miRs). Our
preliminary data suggest that exosomal cargo miRs likely contribute to the therapeutic effect of CEC-exos in
combination with tPA on acute stroke by acting on cerebral endothelial cells to suppress proteins that
promote thrombosis and BBB disruption. We thus propose to develop CEC-exo therapy as an adjunctive
treatment to enhance tPA and thrombectomy treatments of acute ischemic stroke. Aim 1 is to investigate
whether the CEC-exo therapy as an adjunctive treatment enhances tPA and thrombectomy treatments in
aged rats after large artery occlusion. Aim 2 is to investigate whether CEC exosomal cargo miRs
contribute to CEC-exos-amplified thrombolysis leading to reduction of neurovascular damage. Aim 3
investigates whether a special set of CEC-exo cargo miRs contribute to the therapeutic effect CEC-exos on
stroke- induced neurovascular damage by suppressing a network of pro-BBB leakage and thrombotic genes.
Accomplishing these aims will potentially lead to development of a mechanistically based exosome
therapy as an adjunctive treatment to enhance tPA and thrombectomy treatments of acute ischemic stroke,
leading to improvement in the neurological outcome.

## Key facts

- **NIH application ID:** 10335192
- **Project number:** 5R01NS111801-04
- **Recipient organization:** HENRY FORD HEALTH SYSTEM
- **Principal Investigator:** ZHENG GANG ZHANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $395,252
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10335192

## Citation

> US National Institutes of Health, RePORTER application 10335192, Exosome therapy for acute stroke with large artery occlusion (5R01NS111801-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10335192. Licensed CC0.

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