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Mice Models for Peripheral Denervation to Enhance Vascular Regeneration.

Taylor K Brown¹, Caitlyn Dang², Aurea Del Carmen²

¹Department of Biomedical Engineering, Northwestern University, Chicago, Illinois, USA.

Tissue Engineering. Part C, Methods

|March 10, 2025

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This study developed models for sympathetic denervation to investigate its role in vascular repair. Results show ischemia drives vascular regeneration, independent of sympathetic nerve input.

Area of Science:

Neuroscience
Vascular Biology
Regenerative Medicine

Background:

Sympathetic innervation is crucial for vascular function.
Its role in vascular regeneration after ischemic injury is not well understood.
Understanding neural regulation of vascular repair is key for developing new therapies.

Purpose of the Study:

To develop and validate murine models for localized sympathetic denervation.
To investigate the impact of sympathetic nervous system on vascular regeneration and reinnervation following ischemic injury.
To explore the interplay between neural regulation and vascular repair.

Main Methods:

Developed two murine models for sympathetic denervation using 6-hydroxydopamine (6-OHDA): topical application and subcutaneous injections.

Keywords:

6-hydroxydopamine autonomic nervous system chronic limb-threatening ischemia hindlimb ischemia model sympathetic denervation

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Validated denervation duration, vascular impact, and inflammation.

Combined denervation models with a hindlimb ischemia model to study vascular regeneration and perfusion recovery.

Main Results:

Both topical and subcutaneous 6-OHDA methods achieved effective sympathetic denervation with minimal vascular damage or inflammation.
Ischemia led to persistent denervation, with limited sympathetic nerve regeneration observed over 4 weeks.
Microvascular density and perfusion recovery in ischemic muscles were similar in denervated and control groups, suggesting ischemia independently regulates vascular regeneration.

Conclusions:

Localized 6-OHDA administration is a versatile tool for controlled sympathetic denervation in peripheral arteries.
The developed models offer a novel platform for studying vascular regeneration and reinnervation under normal and ischemic conditions.
Ischemic injury appears to govern vascular regeneration independently of sympathetic nervous system input, highlighting potential therapeutic targets in neural-vascular crosstalk.