immune

A new study has discovered a previously unknown structure, a few cells thick, that surrounds the brain. A newfound anatomical structure has been discovered in the brain, which appears to play an essential role in the brain’s waste disposal and immune systems, acting as a protective barrier and harboring immune cells that watch for toxic proteins. Playing a multi-faceted role in the brain’s immunity, the team posits that when this layer of tissue, dubbed the subarachnoid lymphatic-like membrane (SLYM), goes awry, it likely causes many brain disorders such as multiple sclerosis and Alzheimer’s disease. A vast system of interconnected cells and pathways, due to technological advances, the brain is still throwing up amazing discoveries from its fathomless depths – with this latest find taking us on a wondrous journey in and around its entirety. As the realm of the central nervous system (CNS) increases with each new study, a team led by the University of Copenhagen adds to this body of work by discovering a previously unknown protective barrier called the SLYM. The group says the distinct layer, found in both mouse and human brains using two-photon microscopy and dissections, acts as a platform for immune cells such as myeloid cells and macrophages – to monitor the brain for any harmful events that may cause inflammation. Their research, detailed in the journal Science, focuses on the membranes encasing the brain comprising individual layers called the dura, arachnoid, and pia matter. These shields, known collectively as the meninges, keep the brain bathed in the cerebral spinal fluid (CSF), protecting it from the rest of the body and the inflammatory white blood cells held within its bone marrow, blood, and lymph tissue: providing privileged immunity. As part of this exemption, the SLYM dissects the chamber below the arachnoid layer, the subarachnoid space, dividing it into two compartments where it appears to separate freshly made CSF from ‘tainted’ CSF containing waste products and antigens. Therefore, the group state that it is likely involved in the glymphatic system – a network responsible for waste removal in the brain. In their whitepaper, the team state: “SLYM is the host for a large population of myeloid cells, the number of which increases in response to inflammation and aging, so this layer represents an innate immune niche ideally positioned to surveil the cerebrospinal fluid.” Structural immunity The CNS’ privileged immunity also means it does not contain a lymphatic drainage system to flush away antigens and other foreign bodies, so it relies heavily on CSF to carry these unwanted substances to the lymphatic system in the peripheral nervous system. Transported through an extensive network of tubes and compartments all over the brain, CSF acts as a shock absorber for its percipient host while delivering nutrients and carrying away unwanted products. And this is where the SLYM plays a vital role. Sitting in its CSF-filled chamber housing blood vessels and connective tissue joining the arachnoid and pia mater layers, the team state that the new anatomical structure helps control the flow of CSF around the brain, providing us with a “greater appreciation of the sophisticated role that CSF plays not only in transporting and removing waste from the brain, but also in supporting its immune defenses,” said Maiken Nedergaard, co-director of the Center for Translational Neuromedicine in Live Science.  The SLYM itself is only a few cells thick and shares molecular markers with mesothelium, a type of membrane covering other organs in the body, such as the lungs and heart. Mesothelium also plays the role of lubricant between organs that slide against each other. For this reason, the researchers propose that the SLYM is the brain’s mesothelium, lining the connective tissue and blood vessels in the gap between the brain and skull. “Physiological pulsations induced by the cardiovascular system, respiration, and positional changes of the head are constantly shifting the brain within the cranial cavity,” the scientists explain in their whitepaper. “SLYM may, like other mesothelial membranes, reduce friction between the brain and skull during such movements.” Adding to the SLYM’s already extensive immune functionality, experiments in mice also suggest that these diminutive membranes block most proteins, including amyloid plaques that cause Alzheimer’s, from crossing from the ‘contaminated’ CSF compartment to the ‘clean’ CSF compartment–although it allows tiny molecules like electrolytes to pass through. But the large role it plays in neuroprotection has its downsides: The group theorizes that damage to the shield may disrupt its ability to direct these potentially harmful proteins out of the brain. Any damage may also result in immune cells from the skull’s bone marrow flooding the brain’s sterile surface, an interesting finding that could help explain why traumatic brain injuries can cause prolonged brain inflammation and disrupt the normal flow of cleansing CSF. However, they concede that understanding how this disruption impacts the healthy brain “will require more detailed studies.”  “We conclude that SLYM fulfills the characteristics of a mesothelium by acting as an immune barrier that prevents exchange of small solutes between the outer and inner subarachnoid space compartments and by covering blood vessels in the subarachnoid space,” the group write in their paper. Finally, these new findings could uncover vital information pertaining to a host of brain disorders affecting millions of people across the globe – which, the researchers hope, will lead to new targets and therapeutics to aid in their treatment.