Super-resolution ultrasound imaging indirectly reveals neurovascular uncoupling in substantia nigra of a Parkinson’s disease model

Neurovascular coupling contributes to the regulation of cognitive function in Parkinson's disease (PD). However, the correlation between structural and functional integrity of neurovascular unit in substantia nigra and cognitive impairment in PD remains poorly understood. Using super-resolution ultrasound imaging (SRUS), this study aimed to explore the interplay among dopaminergic neurons, microcirculation, and cognitive function in 6-hydroxydopamine-induced PD rat model. The model exhibited impaired motor and cognitive abilities, along with substantia nigra hyperechogenicity detected via transcranial sonography. SRUS revealed reduced microvascular density, complexity, and velocity, alongside increased vessel tortuosity in the substantia nigra. These changes were accompanied by elevated expression of MMP9, CD4, Iba 1, and GFAP, and decreased levels of TH, GLUT-1 and Laminin. Levodopa treatment prevented dopaminergic neurons degeneration, reduced substantia nigra hyperechogenicity, restored microvascular structure and function, as well as alleviated neuroinflammation, which may contribute to improved cognitive performance. These findings suggest that SRUS can effectively detect microvascular alterations in the substantia nigra in a 6-hydroxydopamine-induced PD rat model. Dysfunction neurovascular coupling, likely mediated by dopaminergic neuronal injury, may play a role in PD-related cognitive impairment.