Connections between skull and brain surface (SMCs) confirmed

Skull a gateway to potential treatment for brain diseases such as Alzheimer’s

Alzheimer’s disease, stroke, and multiple sclerosis are just a few of the diseases that cause significant damage through neuroinflammation, an inflammation caused by immune cells. Because of the brain’s protection by the skull bone and surrounding membranes, treating these inflammations is complicated. But researchers have now discovered a connection between the bone marrow of the skull and the brain via small channels. New research reveals that the bone marrow in the skull is unique in its nature and response to disease. This opens new avenues for the diagnosis and treatment of neurological diseases using non-invasive cranial imaging. The new study has now been published in the journal Cell.

Millions worldwide suffer from diseases such as Alzheimer’s, stroke and multiple sclerosis, all of which are characterized by neuroinflammation. This internal, so-called “fire” in the brain, triggered by immune cells and inflammatory molecules, can cause considerable damage. Because of the brain’s protection by the skull and three other protective membrane envelopes, it has been difficult to monitor and control this inflammation. A research team led by Prof. Ali Ertürk of Helmholtz Munich has addressed this challenge in collaboration with experts from Ludwig-Maximilians-Universität München (LMU) and Technische Universität München (TUM).

Direct connections between skull and brain surface established

The latest studies contradict the common belief that there is no direct exchange between the skull and the brain. In fact, connections exist between the bone marrow of the skull and the meninges surface of the brain that facilitate immune cell movement. Researchers have discovered that these connections even run through the robust dura membrane, closer to the brain surface than previously thought. Using tissue clearing and 3D imaging, in which tissue is made transparent, they were able to visualize these channels under the microscope. This allowed for detailed 3D images and comprehensive analysis of structures and cells.

The team also studied the specific function of immune cells in the skull with respect to brain health. They analyzed whether the skull has specific cells and molecules that are not found in other bones. Using transcriptomics (an approach to studying gene expression that involves analyzing thousands of RNA molecules in one at a time) and proteomics in both mice and humans, they found that the skull does indeed harbor unique neutrophil immune cells that are essential in the immune system. “This shows that the connection between the skull and the brain is more complex than previously thought,” emphasized study leader Ilgin Kolabas of Helmholtz Munich.

Prof. Ali Ertürk: “Our results raise hope that this new portal to the brain can transform the treatment of brain diseases.”

Last author Ali Ertürk: “This offers new possibilities in diagnosis and treatment of brain diseases and could fundamentally change our understanding of these conditions. It enables more effective controls for Alzheimer’s disease or stroke and could even prevent their onset through early detection. Our findings raise hope that this newly discovered portal to the brain can transform the treatment of brain disease.”

New opportunities for diagnostics and pathways in treatment

In addition, PET scans have allowed the researchers to uncover that signals from the skull bone are similar to those from the brain, and changes in these signals correlate with disease progression such as Alzheimer’s. In the future, this could allow for easier monitoring of brain inflammation through scans of the head surface.

The research team aims to use noninvasive skull imaging clinically. Ali Ertürk emphasizes the practicality: “Imagine a future where a wearable sensor on the skull can monitor brain health! ” The team is optimistic that this method could optimize diagnosis, monitoring, and possibly treatment of neurological disorders in the future, bringing medicine closer to more effective management of these conditions.