The experimental protocol was approved by the local Ethical Committee for Animal Research (M38-13). Adult male Sprague-Dawley rats (n = 35) (Taconic Copenhagen, Denmark) were used to investigate the brain water content and the permeability-surface area product (PS) for [51Cr]-EDTA. There was a reversed 12–12 light cycle, with darkness during the day. The animals were treated in accordance with the national guidelines for laboratory animals (publications DFS 2004:4, the Swedish Board of Agriculture)