title: Stress does not increase blood-brain barrier permeability in mice.
abstract: Several studies have reported that exposure to acute psychophysiological stressors can lead to an increase in blood-brain barrier permeability, but these findings remain controversial and disputed. We thoroughly examined this issue by assessing the effect of several well-established paradigms of acute stress and chronic stress on blood-brain barrier permeability in several brain areas of adult mice. Using cerebral extraction ratio for the small molecule tracer sodium fluorescein (NaF, 376 Da) as a sensitive measure of blood-brain barrier permeability, we find that neither acute swim nor restraint stress lead to increased cerebral extraction ratio. Daily 6-h restraint stress for 21 days, a model for the severe detrimental impact of chronic stress on brain function, also does not alter cerebral extraction ratio. In contrast, we find that cold forced swim and cold restraint stress both lead to a transient, pronounced decrease of cerebral extraction ratio in hippocampus and cortex, suggesting that body temperature can be an important confounding factor in studies of blood-brain barrier permeability. To additionally assess if stress could change blood-brain barrier permeability for macromolecules, we measured cerebral extraction ratio for fluorescein isothiocyanate-dextran (70 kDa). We find that neither acute restraint nor cold swim stress affected blood-brain barrier permeability for macromolecules, thus corroborating our findings that various stressors do not increase blood-brain barrier permeability.
authors.affiliation: Brain Research Institute, Neuroscience Center Zurich, ETH Zurich, University of Zurich, Winterthurerstrasse, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Roszkowski
authors.affiliation: Brain Research Institute, Neuroscience Center Zurich, ETH Zurich, University of Zurich, Winterthurerstrasse, Zurich, Switzerland bohacek@hifo.uzh.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bohacek
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002199:Capillary Permeability / Q000502:physiology*; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000502:physiology; D003080:Cold Temperature; D003345:Corticosterone / Q000097:blood; D003911:Dextrans / Q000493:pharmacokinetics; D005260:Female; D019793:Fluorescein / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006624:Hippocampus / Q000098:blood supply; D008297:Male; D008810:Mice, Inbred C57BL; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*; D013550:Swimming; D013997:Time Factors
chemical_list: D003911:Dextrans; D005456:Fluorescent Dyes; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein; D003345:Corticosterone
keywords: basic science stress; blood–brain barrier; hippocampus; hypothermia; neurovascular unit