Real-Time and High-Resolution NIR-II-L Imaging of Netrin-1-Mediated Neurovascular Coupling Driven by Dose-Dependent...

Accumulating evidence implicates that disrupted ovarian neurovascular coupling is a vital driver for polycystic ovary syndrome. Electroacupuncture (EA), as a form of peripheral neuromodulation, offers a potential therapeutic avenue to restore this coupling and improve ovarian function. However, how neural regulation leads to vascular changes remains unclear. Conventional histological and imaging methods cannot capture either immediate or long-term effects of EA on neurovascular dynamics, as they are limited by the lack of real-time and continuous in vivo visualization. Here, core-shell lanthanide nanocrystals α-NaYbF₄:2%Er,2%Ce@NaYF₄ showed deep-tissue penetration in the second near-infrared long-wavelength region (NIR-II-L, 1500-1900 nm). Moreover, it could achieve real-time and high-resolution visualization of EA-induced structural and functional changes in the ovarian blood vessels. Our results showed that immediate EA (iEA) at specific parameters and acupoints transiently induced ovarian vasodilation, while cumulative EA (cEA) further strengthened sympathetic-vascular coupling, leading to sustained improvements in local perfusion and follicular development. Additionally, we validated that these effects were dependent on the neurovascular coupling mediator Netrin-1, an axon guidance molecule increasingly recognized for its role in arterial innervation and blood flow regulation in peripheral organs. This study elucidated parameter-specific mechanisms by which EA regulated ovarian function and proposed a visualizable strategy for in vivo analysis of neurovascular structural-functional remodeling.