Evaluation of the effect of stress on the blood-brain barrier: critical role of the brain perfusion time

The Gulf war syndrome has drawn increased attention in the issue of the eff ect of stress on the blood-brain barrier (BBB). We have applied various str essful modalities and tested BBB disruption as measured by the amount of Ev ans blue (EB) retained by brain parenchyma. We have evaluated the retention of this marker as a function of the perfusion time of the brain following stress. This was done to distinguish between the marker retained in the lum en of small blood vessels and the marker retained by the brain parenchyma. Mice were exposed to either short swim stress or restraint stress. In mice exposed to either swim or restraint stress that were perfused for 1 min, th e amount of EB retained in the brain was significantly higher as compared t o non-stressed controls. Fifteen min perfusion markedly reduced the EB brai n content to levels found in the non-stressed animals. In rats exposed to n eural or metabolic stressful stimuli and perfused for 15 min, the EB conten t was similar to non-stressed controls. Our results demonstrate that variou s stress modalities have no effect on the BBB permeability and insufficient wash of blood vessels by perfusion may cause misinterpretation of permeabi lity studies. (C) 2001 Elsevier Science B.V. All rights reserved.