High-Resolution Brain Maps: Vascular Blueprint for Healthy Aging

There are more benefits to healthy blood arteries than just heart health. According to a recent study done by Penn State researchers, vascular health is essential for brain health and may help treat neurodegenerative diseases like Alzheimer’s disease as well as age-related cognitive decline. The results suggest that the brain’s vascular network, often known as its energy infrastructure, may have a crucial and little-studied function in the development of neurodegenerative diseases.

By employing cutting-edge imaging methods, the group created maps of a mouse brain that show how blood vessels and other vascular systems alter with age and pinpointed regions that are susceptible to degradation. Neurons, which are the brain’s nerve cells, become malnourished as blood arteries deteriorate, which leads to their dysfunction or eventual death. It can result in symptoms like sleep disturbance and vascular dementia, which is the second most common cause of cognitive impairment in older persons.

“With something like Alzheimer’s disease, by the time you can see vascular changes and significant brain shrinkage on an MRI, cell death has already occurred. We need to understand how these cells and structures change before a major catastrophe happens. This study provides early signs of neurodegenerative disorders, potentially leading to earlier diagnosis and clues for how we can slow down the aging process and cognitive changes.”- Yongsoo Kim, Study Senior Author and Associate Professor, College of Medicine, The Pennsylvania State University

Kim claims that one of the main causes of neurodegenerative diseases is aging.

“Yet, we really don’t have a good baseline understanding of how normal aging itself changes the brain, particularly the brain’s vasculature,” Kim stated. And with the aging population in the United States growing, he said it’s critical to understand these changes, especially within the network of blood vessels.

Blood arteries, particularly microvessels, control the flow of oxygen, energy, and waste products to and from neurons. Despite their significance, the majority of current study, according to Kim, focuses more on how the structure and function of neurons deteriorate with time than on the vasculature. When scientists have investigated the brain’s vasculature, they have either looked at larger blood veins or concentrated on the somatosensory cortex, a particular, easily accessible area of the brain. More crucially, Kim says that standard neuroimaging methods such as magnetic resonance imaging (MRI) do not offer high enough resolution to discern the intricacies of the microscopic blood veins that comprise 80% to 85% of the brain’s vasculature.

Two high-resolution 3D mapping techniques were used by Kim and the research team to produce a detailed map of the vascular network of the entire mouse brain: light sheet fluorescence microscopy, which images intact 3D samples to visualize the entire brain at a single cell-resolution, and serial two-photon tomography, which produces a series of stacked 2D images. To map the vascular changes that occur in the brain during normal aging, researchers examined the brains of young and elderly mice.

“Because we’re doing high-resolution mapping with the sufficient resolution, we can reconstruct the whole vascular structure and scan the entire brain to pinpoint areas that undergo selective degeneration with age,” Kim said. “What we found is that the area that most people study showed the least amount of change, whereas profound change happens in areas in the deep areas of the brain. This suggests that we’ve been looking at the wrong area when it comes to aging studies.”

The pictures demonstrated that the brain’s vascular network alters in different places. Instead, they were primarily found in the hippocampal network, deep cortical layers, and basal forebrain, indicating that these regions are more susceptible to vascular degeneration. These areas are involved in processing and storing memories, sleep, and attention, among other things.

Vascular length and branching density in the brain decline by around 10% with age, suggesting a sparser blood distribution network. According to Kim, arteries in older brains also seem more twisted than those in younger brains, which can obstruct blood flow, particularly to regions of the brain that are farther from the main arteries, such as the deep cortical layers.

The group also looked at functional alterations in the vasculature and discovered that older brains have slower system responses. This indicates that it is unable to supply the neurons with energy as fast and easily as the cells may require. Pericytes, a kind of cells that control blood flow and blood vessel permeability, are also lost. Blood arteries consequently become “leaky,” endangering the blood-brain barrier.

The group’s earlier work, which revealed the vasculature of a juvenile mouse brain, is expanded upon in this paper. Subsequently, they are investigating how alterations in the brain brought on by Alzheimer’s disease affect neuronal function and vascular health. In the end, they expressed hope that their research will result in neurodegenerative disease treatments.

For more information: Aging drives cerebrovascular network remodeling and functional changes in the mouse brain, Nature Communications, https://doi.org/10.1038/s41467-024-50559-8