9 days after birth: visualization in mice of bone marrow pouches connected to the meninges by vascularized bone channels. Cell nuclei are visualized in cyan (DAPI) and vascularization in magenta (CD146). © Elisa Eme-Scolan/Inserm. © Elisa Eme-Scolan/Inserm
The brain may have a rapid defense mechanism against inflammation, according to a new study: tiny channels in the skull bone allow immune cells to travel directly from the skull to the membranes surrounding the brain. Research from the Inserm, CNRS, and Aix-Marseille Université reveals these channels form in the first few weeks of life and their structure can be altered to enhance immune cell passage. Published in Immunity, these preliminary findings—conducted on a mouse model—suggest a novel approach to modulating the brain’s immune defenses by modifying the architecture of the skull bone.
For years, the brain was considered largely isolated from the rest of the body and the immune system. However, recent research has significantly changed this understanding. Scientists now know the brain constantly communicates with the immune system, particularly at its borders, such as the meninges—membranes located between the skull and the brain. These membranes are rich in immune cells that can detect infections, initiate an immune response, and communicate with nerve cells through molecular signals.
The bone marrow within the skull bone communicates with the meninges through microscopic channels within the bone. These channels allow immune cells to quickly migrate from the skull’s bone marrow to the meninges, representing a “fast track” for immune defenses. Understanding these pathways is crucial for developing new strategies to address neurological conditions involving inflammation.
A new study by researchers at the Inserm, CNRS, and Aix-Marseille Université, at the Centre d’immunologie de Marseille-Luminy, delved deeper into the origins of this communication pathway. Previously, the development of these channels had not been explored.
Using markers that specifically bind to bone channels, scientists observed their formation in a mouse model. They discovered these bone channels primarily develop during the neonatal period, in the weeks following birth. This period also coincided with high activity of specialized cells called osteoclasts, which are responsible for bone resorption.
Based on these findings, the researchers hypothesized they could influence the construction of bone channels during their development by targeting osteoclast activity. Using various pharmacological approaches in a mouse model, they were able to stimulate or inhibit the activity of these cells. They found that stimulating osteoclast activity during the identified neonatal period altered the structure of the skull’s bone channels. The more osteoclast activity was stimulated, the more the channel structures were modified and increased in size.
The scientists proposed that remodeling these bone channels could influence the passage of immune cells from the skull’s bone marrow to the meninges, potentially enhancing their migration in the context of inflammation.
To test this hypothesis, they measured the number of immune cells found in the meninges of mice with a viral infection of the nervous system after remodeling their skull bone channels. Their results showed that modifying the structure of the bone channels directly influenced the intensity of the immune response in the meninges: the more the channels were remodeled—particularly by increasing their size—the more immune cells were found in the meninges.
These observations suggest that remodeling the skull bone facilitated the passage of immune cells to fight the infection.
“These results still require to be confirmed, as they are currently based on mouse models. However, they offer promising perspectives by highlighting the potential of targeting skull architecture as a therapeutic strategy to modulate neuro-immune interactions at the brain’s borders,” explains Elisa Eme-Scolan, a doctoral student and first author of the study.
“Our hypothesis is that by targeting the remodeling of the skull and bone channels, at any age, it may be possible to fine-tune the immune response during neuro-inflammation, whether it involves infections, neurodegenerative diseases, or autoimmune disorders,” explains Réjane Rua, Inserm research director at CIML and the study’s last author.
