A common feature of stroke is neuroinflammation, which can cause severe damage by activation of immune cells and release of inflammatory molecules. However, because of 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) are working on a solution to address this unmet need.
The Intricate Connection Between the Skull and Brain
Recent studies have showed 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 to and from.
The team of scientists discovered 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.
In order to achieve these findings, the team utilised a specialised method known as tissue clearing in combination with 3D imaging to visualise the conduits. During the tissue clearing process biological tissues are treated with a specific solution to render them transparent, allowing for 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 harbours 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 confirmed this – the skull is exceptional, hosting unique neutrophil immune cells, which are a type of white blood cell that play a critical role in the immune system’s defence.
First author of the study Ilgin Kolabas, says: “These findings carry profound implications, suggesting a far more complex connection between the skull and the brain than previously believed.”
Ali Ertürk, corresponding author, adds: “This opens up a myriad of possibilities for diagnosing and treating brain diseases and has the potential to revolutionise 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.”
Envisioning a New Future
Another finding from this research was that by using PET imaging, the researchers found 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.
Looking forward, the researchers envision that their findings could translate to clinical practice in the form of non-invasive skull imaging. Ali Ertürk, says: “This could potentially be done using portable and wearable devices, offering a more accessible and practical way to monitor brain health”.
The team hopes that this approach will greatly improve the diagnosis, monitoring, and possibly even treatment of neurological disorders, bringing us a step closer to more effective management of these devastating conditions.
