title: Blood-brain barrier breakdown occurs early after traumatic brain injury and is not related to white blood cell adherence.
abstract: The time course of blood-brain barrier (BBB) breakdown after traumatic brain injury (TBI) has important implications for therapy. This study was conducted in order to test post-traumatic BBB dysfunction in a model of fluid-percussion induced TBI in rabbits at 1 and 6 hours after TBI and relate it to white blood cell (WBC) activation. Ten anesthetized rabbits had chronic cranial windows implanted three weeks prior to experimentation. Fluid-percussion injury (3.5 atm.) was induced and animals were followed for 1 or 6 h. Intravital fluorescence videomicroscopy was used to assess BBB permeability and WBC adhesion to pial venules. Na(+)-fluorescein was infused continuously over 30 min at either 30 min (Group I, n = 5) or 5.5 h (Group II, n = 5) after TBI. Microvascular permeability in individual postcapillary venules was assessed qualitatively at 1 and 30 min after start of infusion. TBI led to a transient mean arterial blood pressure (MAP) surge after trauma and a progressive increase in the number of sticking WBCs per mm2 vessel wall. Na(+)-fluorescein extravasation was observed in 4 out of 5 Group I animals and in none of Group II. BBB breakdown was not associated with WBC sticking. We conclude that after fluid-percussion injury the BBB is damaged at 1 h post-trauma and that its function is restored 6 h later. Increased WBC sticking at 6 h is not associated with BBB breakdown. Whether WBCs may cause vascular permeability changes at a later point needs further investigation.
authors.affiliation: Aitken Neuroscience Institute and Cornell University Medical College, New York, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Härtl
authors.forename: M
authors.initials: M
authors.lastname: Medary
authors.forename: M
authors.initials: M
authors.lastname: Ruge
authors.forename: K E
authors.initials: KE
authors.lastname: Arfors
authors.forename: J
authors.initials: J
authors.lastname: Ghajar
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001930:Brain Injuries / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D018715:Microscopy, Video; D011817:Rabbits