Tight Junctions and the Blood-Brain Barrier

Abstract

The existence of the blood-brain barrier (BBB) has been recognised for quite some time, but there is still a great deal of confusion among neurobiologists and neurologists as to what it is and how it is regulated. However, there is general agreement that the BBB plays an essential role in influencing the cellular environment in the brain under normal and abnormal conditions. For example, the BBB prevents trafficking of most proteins and even small hydrophilic molecules (including ions) between blood and brain. Situations in which the normal low permeability of the BBB is altered can have serious consequences. For instance, following an ischaemic event, the barrier is disrupted, ions and proteins enter the brain at markedly higher than normal rates, and water molecules follow to maintain osmotic balance. This results in brain oedema, the extent of which is an important determinant of speed of recovery from the initial insult. The barrier is also abrogated, albeit transiently, when cells enter the brain from the blood. This happens in disorders such as multiple sclerosis, caused, presumably, by the entry of activated oligodendrocyte-reactive T-lymphocytes into the brain. Cell trafficking from blood to brain also underlies the formation of metastatic brain tumours. Clearly, then, methods of selectively decreasing BBB permeability would be useful under certain circumstances. However, there is also a great deal of interest in reversibly increasing the permeability of BBB to allow delivery of neuro-therapeutic agents (such as nerve growth factor, which is an anti-degenerative peptide growth factor that might be useful in treating Alzheimer’s disease) to the brain.