Insight into the regulation by second messenger molecules of the permeability of the blood-brain barrier

Recent advances in our knowledge of the blood-brain barrier have in part been made by studying the properties and function of cerebral endothelial cells in vitro. After an era of working with a fraction, enriched in cerebral microvessels by centrifugation, the next generation of in vitro blood-brain barrier model systems was introduced, when the conditions for routinely culturing the endothelial cells were established. This review summarizes the results obtained mainly from this in vitro approach. Different elements of the intracellular signaling messenger systems have been detected in the course of our studies in the cerebral endothelial cells. It has been shown that the synthesizing enzymes of and substrate proteins for the second messenger molecules are present in the cerebral endothelial cells, and their activity and/or amount can change in pathological circumstances, i.e., during the formation of brain oedema. Pharmacological treatments interfering with the second messenger systems proved to be effective in the prevention of brain oedema formation.