New Aspects of Anatomy and Immunology of the CNS and the Skull: A Concise Review

The central nervous system (CNS) has long been considered an immune-privileged organ, shielded behind the blood–brain barrier and lacking conventional lymphatic drainage. Over the past decade, a series of landmark discoveries has fundamentally reshaped this view. The identification of the glymphatic system, meningeal lymphatic vessels, direct vascular channels connecting skull bone marrow to the meninges, a fourth meningeal layer, and arachnoid cuff exit (ACE) points has revealed an unexpectedly rich anatomical and immunological interface between the brain, its surrounding membranes, and the skull. The skull bone marrow has emerged as a specialized hematopoietic niche that supplies myeloid and lymphoid cells to the meninges and CNS parenchyma, while the dural sinuses function as neuroimmune interfaces where CNS-derived antigens are surveyed by patrolling T cells. Together with other cerebrospinal fluid and interstitial fluid clearance routes, these structures form an integrated brain clearance system. This review synthesizes these advances, examines their implications for neurological disease, discusses their potential clinical relevance, and highlights the controversies and open questions that remain.