Astrocytes and Their Role in Formation and Maintenance of the Blood Brain Barrier, Michelle Olsen, Ph.D.
The blood brain barrier (BBB) is composed of specialized endothelial cells. Unlike in the periphery which allows relatively free diffusion through paracellular spaces (the gaps between cells), the spaces between endothelial cells in the central nervous system are completely sealed by tight junctions. These tight junctions serve as barriers, limiting the movement of non-lipophilic substances into the brain. Pericytes, a basement membrane and astrocytic endfeet complete the structure we think of as the BBB. The BBB maintains a 'privileged' environment unique to the central nervous system preventing entry to many substances commonly found in the bloodstream and at the same time allowing access to nutrients and metabolites to meet the high energy demands of the brain.
The intimate relationships of astrocytic endfeet which envelop approximately 99% of vessel and capillary structures of the mature BBB have long suggested astrocytes serve some role in maintaining its functions. Data from numerous laboratories suggest that a combination of soluble factors released from astrocytes as well as physical apposition of astrocytic endfeet to capillary endothelium are required for maintenance and improve BBB function (for review see, Haseloff et al., 2003, Abbott et al., 2006). Data from in vitro studies suggest the presence of astrocytes increases paracellular resistance (a measure of tight junction 'tightness'), and can modulate the expression and localization of endothelial cell transporters.
The role astrocytes play in BBB formation is currently unclear. Tight junctions begin to form relatively early in development, before the presence of astrocytes. Furthermore, it appears that glia cell development itself is somewhat dependent on contact with brain vasculature. Astrocyte-blood vessel contact at the pial surface induces astrocyte differentiation (Zerlin and Goldman, 1997). In vivo the development of a mature BBB is a complex multi-step process that includes the presence of several cell types and secreted factors. Several models are currently being used to further elucidate the role of astrocytes in BBB formation and maintenance.
Haseloff, R.F, Blasig, I.E., Bauer, H. C., Bauer, H. (2005) Cell. and Molec. Bio. 25, 25-39.
The blood brain barrier (BBB) is composed of specialized endothelial cells. Unlike in the periphery which allows relatively free diffusion through paracellular spaces (the gaps between cells), the spaces between endothelial cells in the central nervous system are completely sealed by tight junctions. These tight junctions serve as barriers, limiting the movement of non-lipophilic substances into the brain. Pericytes, a basement membrane and astrocytic endfeet complete the structure we think of as the BBB. The BBB maintains a 'privileged' environment unique to the central nervous system preventing entry to many substances commonly found in the bloodstream and at the same time allowing access to nutrients and metabolites to meet the high energy demands of the brain.
The role astrocytes play in BBB formation is currently unclear. Tight junctions begin to form relatively early in development, before the presence of astrocytes. Furthermore, it appears that glia cell development itself is somewhat dependent on contact with brain vasculature. Astrocyte-blood vessel contact at the pial surface induces astrocyte differentiation (Zerlin and Goldman, 1997). In vivo the development of a mature BBB is a complex multi-step process that includes the presence of several cell types and secreted factors. Several models are currently being used to further elucidate the role of astrocytes in BBB formation and maintenance.