Mouse models of neurological disorders: a view from the blood-brain barrier

The number of disease models that involve an aspect of blood-brain barrier (BBB) dysregulation have increased tremendously. The main factors contributing to this expansion have been an increased number of diseases in which the BBB is known to be involved, an increase in the known functions of the BBB, and an increase in the number of models and tools with which those diverse functions can be studied. In many cases, the BBB may be a target of disease; current thinking would include hypertensive encephalopathy and perhaps stroke in this category. Another category are those diseases in which special attributes of the BBB may predispose to disease; for example, the ability of a pathogen to cross the BBB often depends on the pathogen's ability to invoke transcytotic pathways in the brain endothelial or choroid plexus cell. Of special interest are those diseases in which the BBB may be the primary seat of disease or play a major role in the onset or progression of the disease. An increasing number of diseases are so categorized in which BBB dysfunction or dysregulation plays a major role; this review highlights such roles for the BBB including those proposed for Alzheimer's disease and obesity.