Neurological diseases cause severe damage due to neuroinflammation mediated by immune cells. Managing this inflammation poses a challenge because the brain is protected by the skull and additional surrounding membranes that make the brain less accessible for treatment approaches. Now, new research has revealed that cells in the skull’s bone marrow are unique in their disease response, which offer new possibilities for the diagnosis and treatment of neurological diseases.

A team of scientists led by Prof. Ali Ertürk at Helmholtz Munich, PhD, in collaboration with researchers from the Ludwig-Maximilians-Universität München (LMU) and the Technical University of Munich (TUM) sought to address this unmet need.

The findings are published in Cell in an article titled, “Distinct molecular profiles of skull bone marrow in health and neurological disorders.”

“The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear,” the researchers wrote. “Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature.”

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. The team utilized a method called tissue clearing in combination with 3D imaging to visualize the conduits. As a result, 3D images of structures and cells were generated, leading to a comprehensive visual analysis.

The research team dove 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 demonstrated the skull hosts unique neutrophil immune cells. “These findings carry profound implications, suggesting a far more complex connection between the skull and the brain than previously believed,” highlighted the first author of the study Ilgin Kolabas, a PhD student at the Ertürk lab at Helmholtz Munich.

“This opens up a myriad of possibilities for diagnosing and treating brain diseases and has the potential to revolutionize our understanding of neurological diseases,” added Ertürk. “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.”

The researchers hope that their findings could translate to clinical practice in the form of non-invasive skull imaging. “This could potentially be done using portable and wearable devices, offering a more accessible and practical way to monitor brain health,” explained Ertürk.

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