Scientists had previously discovered pathways going from the bone marrow of the skull towards the brain, allowing immune cell movement. Now, new research revealed that cells in the skull’s bone marrow are unique in their composition and in their disease response. These findings offer new possibilities for the diagnosis and treatment of neurological diseases and revolutionize brain health monitoring in the future with non-invasive skull imaging. The results are now published in Cell.
Neurological diseases such as Alzheimer's, stroke, and multiple sclerosis have a devastating impact on the lives of millions worldwide. A common feature is neuroinflammation, an internal "fire" in the brain that can cause severe damage by activation of immune cells and release of inflammatory molecules. However, due to the brain's relative inaccessibility, as it is shielded by the skull and three additional layers of protection in the form of membranes, controlling and monitoring this inflammation has been a major challenge. A team of scientists around Prof. Ali Ertürk at Helmholtz Munich in collaboration with researchers from the Ludwig-Maximilians-Universität München (LMU) and the Technical University of Munich (TUM) sought to address this unmet need.
Not Just a Helmet: The Intricate Connection Between the Skull and Brain
Defying traditional understanding that the skull and the brain have no direct interchange, recent studies have unveiled direct connections between the skull's bone marrow and the brain's outermost surface of the protective membranes, the meningeal surface. These connections act as conduits, facilitating the movement of immune cells back and forth. The team of scientists found that these connections often traverse even through the outermost and toughest layer of membrane, the dura, opening up even closer to the brain surface than previously thought. To achieve these significant findings, the team utilized a specialized method called tissue clearing in combination with 3D imaging to visualize the conduits. During the tissue clearing process biological tissues are treated with a specific solution to render them transparent enabling the passage of light for the examination of both brain tissue and the skull under a microscope. As a result, 3D images of structures and cells were generated, leading to a comprehensive visual analysis.
The research team probed even deeper into the distinct role the skull-based immune cells play in brain physiology and diseases. They began by questioning if the skull harbors unique brain-specific cells and molecules that cannot be found in other bones. Extensive analysis of the RNA and protein content in the form of transcriptomics and proteomics analyses of both mouse and human bones affirmed this - the skull is indeed exceptional, hosting unique neutrophil immune cells, which are a type of white blood cell that play a critical role in the immune system's defense. "These findings carry profound implications, suggesting a far more complex connection between the skull and the brain than previously believed” highlights the first author of the study Ilgin Kolabas, Ph.D.-student at the Ertürk lab at Helmholtz Munich.
Ali Ertürk, corresponding author, adds: “This opens up a myriad of possibilities for diagnosing and treating brain diseases and has the potential to revolutionize our understanding of neurological diseases. This breakthrough could lead to more effective monitoring of conditions such as Alzheimer's and stroke, and potentially even aid in preventing the onset of these diseases by enabling early detection.”
MEDICA-tradefair.com; Source: Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH)
