International Business Department           Liu Bojia           August 16, 2023

Alzheimer's disease, stroke, multiple sclerosis ...... Many of the central nervous system diseases that threaten human health have one thing in common: neuroinflammation. Neuroinflammation, like a burning fire, causes serious damage to brain function by activating immune cells to release inflammatory factors.

Yet detecting and controlling the fire in time is difficult because the entire brain is encased in a hard skull and multiple layers of meninges, which hinder the monitoring of neuroinflammation and make it difficult to administer many treatments.

Recently, a team of researchers from Germany made a breakthrough discovery: the actual connection between the skull and brain tissue is much more complex than previously thought, and the skull actually hides an "alarm" that can monitor neuroinflammation.

Many people think of the skull as the equivalent of a hard helmet that fits over the outside of the brain. But new research suggests otherwise.

The study was led by Professor Ali Ertürk of the Helmholtz Munich. In previous work, Professor Ertürk's team has developed several tissue clearing techniques and three-dimensional visualization techniques.

This time, the team took full advantage of these cutting-edge technologies in order to see the fine structures between the skull, meninges and brain tissue. Simply put, tissue removal means that the entire organ can be made transparent while preserving the cellular structure, and when placed under a microscope, light can completely penetrate the skull and brain tissue. Subsequently, combined with 3D imaging, the structural and cellular details of the skull's connection to the meninges are clearly revealed.

As can be seen, the bone marrow of the skull is directly connected to the surface of the outermost layer of the meninges (dura mater), and the channels formed are known as skull-meninges connections (SMC), which allow the immune cells within the bone marrow of the skull to move back and forth.

And these immune cells in the bone marrow of the skull play a unique role in the physiology and pathology of the brain.

The researchers first analyzed the cell types in the mouse skull in detail. Transcriptomics analysis showed that compared to bones in other parts of the body, both in healthy and injured states, skull cells have their own unique molecular signature and possess unique neutrophils - a type of white blood cell that plays a key role in the defense of the immune system.

Further analyzing the bones donated by human volunteers, the results of proteomic analysis again showed that the skull is very unique, with differentially expressed neutrophil-associated pathways and unique synaptic protein profiles.

Not only do skull bone marrow have a unique cellular composition and molecular profile, but even more intriguingly, they may also reflect neuroinflammation in brain disorders. Researchers used TSPO-targeted positron emission tomography (TSPO-PET) to image the cranial bones of patients with Alzheimer's disease, stroke, and other neurological disorders, and found that the imaging results reflect the characteristic neuroinflammatory distributions of each of the different diseases.

In other words, it is possible to monitor brain health and diagnose neurological diseases through non-invasive skull imaging. As Prof. Ertürk summarizes, this breakthrough could lead to new ways to more effectively monitor central nervous system disorders such as Alzheimer's disease, and perhaps even prevent the onset of these diseases through early detection and diagnosis. These prospects will revolutionize the future of brain health monitoring, opening up countless possibilities for diagnosing and treating brain diseases.