New aspects in fenestrated capillary and tissue dynamics in the sensory circumventricular organs of adult brains

The blood-brain barrier (BBB) generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs), which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), and area postrema (AP), have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs) sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF) signaling may be involved in angiogenesis and neurogliogenesis, both of which affect vascular permeability. Thus, recent findings advocate novel concepts for the CVOs, which have the dynamic features of vascular and parenchymal tissues.