Neurovascular Coupling in Neurological Disorders: A Comprehensive Review

This article provides a systematic review of current research on Neurovascular Coupling (NVC), covering its fundamental mechanisms, role in diseases, investigative technologies, and future directions. NVC describes the process where neuronal activity triggers localized changes in cerebral blood flow (CBF). This mechanism is orchestrated by the Neurovascular Unit (NVU), a functional complex comprising neurons, glial cells (e.g., astrocytes), and vascular cells (e.g., endothelial cells, pericytes, vascular smooth muscle cells). These components work in concert through intercellular signaling to co-regulate CBF. The regulation involves various vasoactive substances, including nitric oxide (NO) and prostaglandin E2 (PGE2).Dysfunction of NVC is a critical pathological mechanism in neurological disorders. In Alzheimer's disease, abnormalities across the NVU lead to blood-brain barrier disruption and impaired clearance of amyloid-β, exacerbating cognitive decline. Similarly, in cerebral small vessel disease, endothelial dysfunction manifesting as impaired NVC is a key feature, with severity correlating with structural damage like white matter hyperintensities. Following an ischemic stroke, NVU component abnormalities cause acute NVC decoupling, and the degree of functional recovery is closely associated with neurological prognosis. Technologies for studying NVC are evolving. Established methods include functional Magnetic Resonance Imaging (fMRI), which measures the blood-oxygen-level-dependent (BOLD) signal, and transcranial Doppler ultrasound. Recent advancements feature novel tools like high-speed, large-field-of-view photoacoustic/fluorescence hybrid microscopes (e.g., LiTA-HM), enabling cortex-wide imaging of neurovascular dynamics with subcellular resolution. Current research challenges include reliance on animal models. Future directions should integrate structural and functional neuroimaging techniques. Therapeutically, strategies aimed at enhancing endothelial function to restore NVC hold promise. Combining advanced imaging with omics technologies will likely deepen the understanding of the NVU and propel the field toward precise prevention and treatment of NVC-related diseases.