Relative contributions of a CVO and the microvascular bed to delivery of blood-borne IL-1α to the brain

Diffusion from brain regions lacking a blood-brain barrier (BBB) and saturable transport across capillaries are possible pathways for the entry of blood-borne interleukin-1 alpha into the central nervous system (CNS). To assess the involvement of these putative routes, mice received intravenous injections of radioiodinated interleukin-1 alpha, and their brains were subjected to emulsion autoradiography. The resulting patterns of silver grain distribution showed that diffusion of interleukin-1 alpha from the choroid plexus and the subfornical organ was greatly restricted. These restrictive properties were quantified by the determination of D-1/2 values, the distances needed for the concentration of silver grains to decrease by one-half. Within several brain regions, a subset of the microvasculature indicated transport of interleukin-1 alpha across the BBB. Individual microvessels showed different patterns of transport ranging from robust to absent. The high degree of containment of blood-borne interleukin-1 alpha within the regions lacking a BBB indicates that these sites cannot account for total delivery of the cytokine into the brain and suggests instead that the microvascular network may serve as the major route of entry into the CNS.