While blood vessels in the body itself, such as those that extend toward the legs and the arms, let through a relatively large amount of blood, the vessels found in the brain are much smaller and also considered restrictive. Endothelial cells line up to form what is often called the blood-brain-barrier. This “barrier” helps to ensure that only the necessary oxygen and glucose are sent toward the brain, keeping potentially toxic materials out of the region.
Scientists have known for some time that the activation of a specific receptor known as Adora2a causes a change in how these endothelial cells function. In turn, the blood-brain barrier can be altered, allowing harmful substances to enter the brain.
In a new study, scientists dug further into this matter. Several laboratory rats formed the study subjects. Scientists induced insulin resistance and obesity in the mice through a modified diet approach.
What the scientists found was that obesity led to a chronic activation of the Adora2a receptors on these endothelial cells. In turn, this constantly caused an expansion of blood vessels that lead toward the brain.
At first, small toxic molecules started to enter the brains of these rats. The first molecules that entered the brain was fluorophore sodium fluorescein, also known as NaFl. When insulin resistance developed along with obesity, however, larger molecules eventually started to cross the blood-brain barrier in these mice.
When these toxic molecules enter the brain, it eventually causes damage to the hippocampus. This is a center of the brain that is known to be involved with functions such as memory, as well as learning.
Following these findings, the scientists decided to develop a molecule that would block the activation of the Adora2a receptor on the endothelial cells. They found that with the inhabitation of Adora2a receptor activation, a normal functioning blood-brain barrier was observed.
With the findings of the study, there is new hope for treatments to be developed to assist in possibly reducing the cognitive impairment that is often found among obese people as they age. While all people tend to experience some decline in their cognitive performance, it has been established that those who are obese and people with insulin resistance develop these impairments at a significantly faster rate.
Further studies on human subjects are now called for. This can help scientists determine if the Adora2a receptors can also be blocked effectively in the human body. Additionally, scientists will need to determine if by blocking these receptors an improvement in the maintenance of the blood-brain barrier will be observed.
Read more about the study in the Journal of Neuroscience.