Neurovascular-neuroenergetic coupling axis in the brain: master regulation by nitric oxide and consequences in aging and neurodegeneration.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and preclinical literature without original human data or systematic search methods.
PubMed 28435052 · doi:10.1016/j.freeradbiomed.2017.04.026
What was done
This narrative review synthesized literature examining the role of neuronal-derived nitric oxide in regulating both local cerebral blood flow (neurovascular coupling) and metabolic substrate utilization between astrocytes and neurons (neuroenergetic coupling). The authors reviewed molecular targets such as soluble guanylate cyclase, cytochrome c oxidase, and hemoglobin, and discussed how nitric oxide-driven pathways, including astrocytic glycolysis and lactate shuttling, are altered by redox shifts in aging, traumatic brain injury, epilepsy, Alzheimer's disease, and Parkinson's disease.
What was found
The abstract reports no primary experimental measurements, statistical comparisons, or numerical data. It describes a conceptual framework where nitric oxide produced during glutamatergic activation diffuses across cellular domains to coordinate hemodynamic responses with astrocyte-to-neuron metabolic support, and summarizes how redox balance disruptions shift nitric oxide signaling toward cellular dysfunction across multiple neurodegenerative states.
Why it matters
The paper unifies cerebral blood flow regulation and cellular energy metabolism into a single functional axis governed by nitric oxide. This provides a mechanistic framework for understanding how vascular and metabolic decoupling jointly contribute to age-related cognitive decline and neurodegenerative pathology.
Limits
As a narrative review, the paper presents no systematic search methodology, meta-analytic pooling, or original empirical data. The abstract provides no quantitative metrics, effect sizes, or study counts, and the proposed mechanisms rely on preclinical models without direct clinical verification in human populations.
Cited by
- supports Nitric oxide is involved in cerebral bioenergetics related to glucose utilization and enhances cerebral blood supply.