Blood-Brain Barrier Dysfunction Predicts Progression of Cerebral Small Vessel Disease

Cerebral small vessel disease is characterized by the accumulation of small volumes of damaged tissue in the brain, the results of the rupture or blockage of tiny blood vessels. Researchers here show that the state of the blood-brain barrier predicts the pace at which this damage grows over time. The blood-brain barrier functions to ensure that only certainly molecules and cells can move back and forth from brain and bloodstream, but like all tissues it becomes dysfunctional with age. This contributes to chronic inflammation in the brain, as unwanted substances find their way into the central nervous system. It may be case that blood-brain barrier issues and the breakage of small blood vessels that produces damaged brain tissue are distinct outcomes of the same underlying mechanisms of aging and their downstream effects. To pick an obvious example, the raised blood pressure of age-related hypertension is destructive to blood vessel walls and the delicate tissues that surround them.

"Previous research has shown that disruption of the blood-brain barrier is increased in people with cerebral small vessel disease. People with cerebral small vessel disease also may have brain lesions called white matter hyperintensities. Such lesions are visible by MRI and believed to be signs of brain damage and a marker of the severity of disease. For our study, we wanted to see if a leaky blood-brain barrier was linked to degeneration of brain tissue even before these brain lesions appear. We looked at normal brain tissue, surrounding and close to the brain lesions, because we consider this 'tissue at risk.'"

The study involved 43 people with cerebral small vessel disease with an average age of 68. Researchers used MRI at the start of the study to measure the leakiness of the blood-brain barrier for each participant. They then used another brain imaging technique to measure the integrity of the tissue's microstructure surrounding brain lesions. This imaging technique was repeated two years later to see whether the brain tissue integrity has decreased.

Researchers measured the relationship between blood-brain barrier leakage and changes in brain tissue. They found the higher the tissue volume with blood-brain barrier leakage at the start of the study, the greater the loss of brain tissue integrity was around brain lesions two years later. For every 10% increase in leakage volume at the start of the study, after two years the diffusivity of the brain tissue increased by 1.4%, representing a decrease in brain tissue integrity. They also found a similar relationship involving the leakage rate of the blood-brain barrier - a higher leakage rate at the start of the study resulted in more loss of tissue microstructure around the brain lesions.


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