The Circumventricular Organs

Circumventricular organs (CVOs) are highly vascularized midline structures lacking a complete blood-brain barrier (BBB) due to the presence of fenestrated vasculature, allowing peripheral circulating factors to penetrate the brain and influence neuronal activity. These specialized areas are points of communication between the blood, the brain, parenchyma, and the cerebrospinal fluid (CSF). Neurons and glial cells of the CVOs express a unique repertoire of receptors and ion channels and receive a wide range of chemical signals from the bloodstream. With the remarkable technological improvement on animal and molecular research in recent years, more circumventricular areas are being discovered that are not directly protected by the BBB and that acquire the status of “CVO”; at present, the main organs described being part of this group of substructures are supraoptic nucleus, subfornical organ, neurohypophysis, median eminence, subcommissural organ, area postrema, pineal gland, and organum vasculosum of the lamina terminalis. In this chapter, we review all the main CVOs addressing their anatomy, functionality, and clinical correlates. Indeed, CVOs act as a port of entry, trigger, and propagation of pathogenic stimuli. The morphologic and functional features of the CVOs allow the access of circulating cytokines, immunoglobulins, and infectious agents to these areas, leading to exposure of local neurons, glial and endothelial cells to these signals. The CVOs may recruit circulating inflammatory cells into the brain through upregulation of adhesion molecules in their fenestrated capillaries. In response to these signals, hypothalamic and brainstem neurons initiate the several pathological responses including fever, somnolence, endocrine and autonomic disturbances, anorexia, and vomiting.