# Elucidation of botulinum neurotoxin A mediated cerebral revascularization graft spasmolysis mechanisms

> **NIH NIH R03** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $82,500

## Abstract

Project Summary
The primary goal of this study is to investigate the effects of botulinum toxin A (BTX A) adrenergic and Rho
kinase pathways elucidating, for the first time, its spasmolytic mechanism of action in human cerebral
revascularization grafts. Revascularization graft stenosis and occlusion remains a formidable complication which
can lead to significant morbidity and mortality. Graft stenosis and occlusion from vasospasm is thought to be at
least partially mediated through increased activity in adrenergic vasospastic pathways. Additionally, evidence
supporting the role of the RhoA/Rho kinase (ROCK) pathway in vasospasm has been described. Despite various
proposed spasmolytics, there is no single effective agent. Factors including anatomic and physiologic variability
in revascularization conduits, patient demographics and comorbidities have been associated with graft
vasospasm pathogenesis and response to spasmolytics. Given this knowledge, the ideal spasmolytic agent likely
needs to modulate multiple pathways to exert therapeutic effect.
BTX A is a powerful neurotoxin widely used in clinical practice for the treatment of a variety of spastic conditions.
Although its classic paradigm of cholinergic neural transmission blockade has been widely accepted, evidence
for other possible mechanisms has been described. Other mechanisms involving modulation of adrenergic,
ROCK and endothelial vasomotor pathways has been reported in animal studies. Recently, our group published
the first pilot study describing use of BTX A for cerebral revascularization graft spasm prevention.
The proposed study will utilize leftover arterial tissue samples collected pre- and post-BTX A treatment during
cerebrovascular bypass surgery. We have recently established an Institutional Review Board approved fresh-
frozen vascular tissue bank where the vascular tissue samples are stored and can be retrieved for research
purposes. Targeted tissue, protein and molecular level analyses of BTX A effects on two major vasospastic
pathways will be performed utilizing core facilities and research laboratories affiliated with our institution.
Elucidating the mechanism of action for BTX A spasmolysis will help to fill a current gap in knowledge between
human and animal studies and could provide the basis for a phase 2 clinical efficacy study. These findings also
have the potential to expand the use of BTX A for vasospastic complications in cardiac revascularization and
reconstructive surgery. Our basic science collaborations, vascular tissue bank and high clinical volume make
our Cerebral Revascularization center a unique environment to perform this research.

## Key facts

- **NIH application ID:** 9917850
- **Project number:** 5R03NS113090-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Jonathan Joseph Russin
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $82,500
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917850

## Citation

> US National Institutes of Health, RePORTER application 9917850, Elucidation of botulinum neurotoxin A mediated cerebral revascularization graft spasmolysis mechanisms (5R03NS113090-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9917850. Licensed CC0.

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