The brain depends on a constant supply of oxygen, delivered through an intricate network of tiny blood vessels. Unlike other organs, it has little energy stored and is particularly sensitive to interruptions in blood flow. While it is known that blockages in larger vessels can have devastating consequences, less is understood about the effects of momentary stalls in the smallest vessels, the capillaries. These stalls have been observed more often in aging and in conditions such as Alzheimer's disease, stroke, and traumatic brain injury.
A new study led by researchers at Boston University and Massachusetts General Hospital shows that even brief interruptions in capillary flow can cause rapid, localized drops in oxygen that likely extend into nearby brain tissue. The study is published in Neurophotonics . Using advanced two-photon phosphorescent lifetime microscopy, the team measured red blood cell passage and oxygen levels in more than 300 capillaries in awake mice. This technique allowed them to track stalls—moments when red blood cells temporarily stop moving through a vessel—and monitor the resulting oxygen changes in real time.
The results were striking. Every stall caused an immediate decline in oxygen within the capillary, which would likely spread into surrounding tissue. About 40 percent of stalls dropped to levels considered hypoxic, and a quarter fell to critically low levels below 5 mmHg, where cells cannot sustain normal energy production. These effects could not be predicted from how much blood normally flowed through a capillary, its baseline oxygen level, or its location in relation to larger arteries and veins.
Interestingly, the severity of hypoxia differed depending on the animal's state. In mice under anesthesia, stalls were less likely to cause dangerously low oxygen, because the anesthetic both dilates blood vessels and reduces the brain's metabolic demand. In contrast, awake animals were far more vulnerable, highlighting how dependent the brain is on uninterrupted microvascular flow under normal conditions.
The researchers also found hints that stalls can affect nearby capillaries, which sometimes showed small drops in oxygen when a neighboring vessel stopped flowing. This suggests that the impact of a stall may ripple outward, disrupting not just the blocked vessel but the surrounding microvascular network. But more data needs to be collected.
Because some capillaries tend to stall repeatedly, the findings raise concerns that tissue in their vicinity may experience repeated bouts of hypoxia over time. This could provide an additional mechanism for how capillary dysfunction contributes to brain diseases where stalling is common.
The authors note that their study was limited to relatively shallow cortical layers and healthy animals, but the approach opens the door to deeper investigations and studies in disease models. Understanding when and where these stalls occur, and how they create pockets of low oxygen, could be key to uncovering new pathological pathways in conditions from dementia to stroke.
For details, see the original Gold Open Access article by J. Giblin et al., " Brief disruptions in capillary flow result in rapid onset of hypoxia ," Neurophotonics 12(S2), S22803 (2025), doi: 10.1117/1.NPh.12.S2.S22803 .
