Microglia, the brain's immune cells, play a pivotal role not only in maintaining brain health but also significantly affect blood flow throughout the brain. Recent research conducted at the University of Virginia has uncovered how these cells use the ectonucleotidase CD39 to modulate cerebral blood flow (CBF) via the conversion of adenosine triphosphate (ATP) to adenosine.
The study, published on September 9, 2025, reveals novel insights on neurovascular coupling—a complex process ensuring the brain receives adequate oxygen and nutrients according to its activity. Researchers found microglia regulate both the baseline levels of CBF and its response to various stimuli, such as sensory activity.
Most intriguingly, it was observed through the study's findings, "notably, microglia repopulation corrects these cerebral blood flow anomalies." This hints at the adaptive capacity of microglia following disturbances to their population, emphasizing their role as key regulators of vascular responses.
The research employed advanced imaging techniques, including laser speckle imaging, to assess changes in blood flow. This was coupled with pharmacological interventions and genetic modifications to investigate the specific mechanisms by which CD39 facilitates the conversion of ATP to adenosine, affecting CBF.
Overall, the results suggest, "together, these results suggest the microglial CD39-initiated breakdown of extracellular adenosine triphosphate co-transmitter is an important step in neurovascular coupling." This emphasizes how microglia serve as more than mere defenders against pathogens; they actively participate in maintaining cerebral circulation dynamics.
While earlier studies hinted at the role of microglia and ATP metabolism, this research delineates their exact contributions to neurovascular function. With microglial inflammation associated with numerous neurological disorders, including stroke and neurodegeneration, the identified mechanism through CD39 opens new avenues for targeted therapies.
To conclude, this research establishes microglia as fundamental players within the complex network of neurovascular regulation. The potential therapeutic avenues derived from these findings were articulated poignantly as the authors stated, "our results indicate microglia play an important role in CNS purinergic signaling via CD39-dependent catalysis of extracellular ATP to AMP and adenosine." This highlights the dual role of microglia as protectors of neural integrity and modulators of physiological processes.