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Bypassing the blood-brain barrier

The meninges membranes surrounding the brain are an immune-blood-brain interface in homeostasis and disease Brain function requires tight regulation of the cerebral microenvironment, an outcome achieved through specialized brain barriers. The presence of these barriers and the observation that skin grafts transplanted into the brain are poorly rejected (1) helped establish the dogma that the central nervous system (CNS) is immune privileged; that is, immune responses are not elicited against antigens originating from the CNS. However, recent studies have identified entry and exit points for immune cells, cytokines, and brain-derived antigens or waste molecules through distinct anatomical routes in the meninges (a triple-layered membrane that surrounds the brain parenchyma). These meningeal “backdoors” might allow for blood-brain barrier (BBB) bypass, providing an interface for peripheral immune system interaction with the CNS, and could play an important role in neuroinflammation and neurodegeneration.