Evidence for cellular and solute passage between the brain and skull bone marrow across meninges: A systematic review

A potential two-way passage of cells and substances between the brain and skull bone marrow may open for new insights into neurological disease. The arachnoid membrane was traditionally considered to restrict cells and larger molecules in CSF from entering the dura and bone marrow directly. However, new data on exchange between brain and skull bone marrow have recently emerged. Here, we conducted a systematic literature to answer the question: What is the current evidence regarding the movement of cells and molecules between the brain and skull bone marrow, spanning CSF and meninges? We excluded studies related to head or skull trauma, cranial fractures or defects, cancer invasion, CSF leakage, spontaneous intracranial hypotension, spinal dura mater, and studies solely focusing on meningeal lymphatic vessels or the passage of substances from CSF to meningeal lymphatic vessels. The review identified 16 studies that provide evidence of communication between the brain, meninges and skull bone marrow. Cells (such as B and T cells and neutrophils), bacteria, and substances (tracers, drug compounds) have been reported to pass between the brain and skull bone. However, most studies are performed in rodents, emphasizing the need for translation to humans.