Neuromodulation of Cerebral Blood Flow: A Physiological Mechanism and Methodological Review of Neurovascular Coupling, 2025, Zhong et al

[Mij]

Abstract ​

Neurovascular coupling (NVC) refers to the dynamic regulation of cerebral blood flow via neuronal activity, a mechanism crucial for maintaining normal brain function. This review elucidates the intricate physiological mechanisms underlying NVC, emphasizing the coordinated roles of neurons, glial cells, and vascular cells in mediating activity-induced changes in blood flow.

We examine how NVC is impaired in neurological disorders such as Alzheimer’s disease and stroke, where the dysfunction of this coupling contributes to neurodegeneration and neurological deficits. A broad range of techniques for assessing NVC is discussed—encompassing the established modalities like transcranial Doppler, near-infrared spectroscopy, and functional magnetic resonance imaging (fMRI), as well as emerging technologies such as functional ultrasound imaging and miniaturized endoscopy that enable high-resolution monitoring in deep brain regions.

We also highlight the computational modeling approaches for simulating NVC dynamics and identify the novel biomarkers of NVC dysfunction with potential utility in early diagnosis. Finally, emerging translational applications—including neuromodulation techniques and targeted pharmacological interventions—are explored as means to restore normal neurovascular function.

These advancements underscore the clinical significance of NVC research, paving the way for improved diagnostic tools and therapeutic strategies in neurological disorders.
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[Mij]

How it Works

1. Neuronal Activation: When neurons become active, they release signaling molecules.
   
   
2. Vasoactive Agents: These molecules, such as nitric oxide (NO) and arachidonic acid metabolites, cause blood vessels to relax and expand.
   
   
3. • Increased Blood Flow: This vasodilation leads to a local increase in cerebral blood flow (CBF).
     
   • Energy Supply: The increased blood flow delivers more oxygen and glucose to the active brain area, matching its increased energy demand.
     

Importance of NVC

• • Energy Matching: NVC ensures that the brain has the energy it needs to function properly.
    
  • Neuroimaging: It is the foundation for non-invasive techniques like BOLD functional magnetic resonance imaging (fMRI), which detects changes in blood flow and oxygen levels to map brain activity.
    
  • Development: NVC undergoes maturation during development, as seen in the negative BOLD signals observed in infants compared to adults.
    

Disruption and Disease

• • Neurovascular Uncoupling:
    When NVC is disrupted, there is a disconnect between neural activity and blood flow.
    
  • Causes:
    This can occur in various neurological conditions, including Alzheimer's disease, stroke, and traumatic brain injuries like concussions.
    
  • Symptoms:
    Disrupted NVC can lead to symptoms of energy deprivation in the brain, such as fatigue, headaches, and brain fog.