9 Aug 2023
Cells in the skull’s bone marrow are unique in their composition and in their disease response, researchers led by Ali Ertürk show. These findings offer new possibilities for the diagnosis and treatment of neurological diseases.
In the bone marrow of the skull: Immune cells stained in blue and vessels in pink. | © Erturk Lab
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 at Helmholtz Munich, LMU and Technical University of Munich (TUM) led by Prof. Ali Ertürk sought to address this unmet need. Ertürk is Head of the Institute for Tissue Engineering and Regenerative Medicine (iTERM) at Helmholtz Munich and Professor at the Institute for Stroke and Dementia Research (ISD), LMU University Hospital.
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. Utilizing a specialized method called tissue clearing in combination with 3D imaging, 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.
The research team probed even deeper into the distinct role the skull-based immune cells play in brain physiology and diseases and questioned, 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.”
Another impactful finding was that using PET imaging, the researchers discovered that signals from the skull mirrored those from the underlying brain, with changes in these signals corresponding to disease progression in patients with Alzheimer's and stroke. Thereby showcasing a new potential to monitor brain inflammation simply by scanning the surface of the patient’s head.
Ilgin Kolabas et al.: Distinct molecular profiles of skull bone marrow in health and neurological disorders. Cell, 2023