title: Reoxygenation stress on blood-brain barrier paracellular permeability and edema in the rat.
abstract: The blood-brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1 h) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 h time course in conjunction with paracellular permeability, gray matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of (14)C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6-18 h time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min-1 h reoxygenation time points; and the second increase at only the 24 h time point. Analysis of serum derived cytokines (IL-1beta, TNFalpha, IL-6, IL-10, and IFNgamma) demonstrated that only IL-1beta and IL-6 were at detectable levels, but these levels were similar to controls. White blood cell counts showed significant decreases in lymphocytes (10 min-3 h), increases in monocytes (10 min-3 h and 12 h), and increases in polymorphonuclear cells (1 h and 3 h). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.
authors.affiliation: Pharmaceutical Sciences, School of Pharmacy, Southern Illinois University Edwardsville, Campus Box 2000, University Park Drive, Edwardsville, IL 62026, USA. kwitt@siue.edu
authors.forename: Ken A
authors.initials: KA
authors.lastname: Witt
authors.forename: Karen S
authors.initials: KS
authors.lastname: Mark
authors.forename: Karin E
authors.initials: KE
authors.lastname: Sandoval
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Davis
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001929:Brain Edema / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability; D002250:Carbon Radioisotopes; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D007958:Leukocyte Count; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013395:Sucrose / Q000378:metabolism; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D016207:Cytokines; D013395:Sucrose