title: Blood-brain barrier changes during compensated and decompensated hemorrhagic shock.
abstract: Dysfunction of the blood-brain barrier (BBB) can be associated with a large number of central nervous system and systemic disorders. The aim of the present study was to determine BBB changes during different phases of hemorrhagic shock. The experiments were carried out on male Wistar rats anaesthetized with urethane. To produce compensated or decompensated hemorrhagic shock, mean arterial pressure was decreased from the normotensive control values to 40 mmHg by a standardized method of blood withdrawal from the femoral artery. Cerebral blood flow changes were followed by laser-Doppler flowmetry, and arterial blood gas values were monitored over the whole procedure. Cortical blood flow was significantly reduced in compensated and in decompensated hemorrhagic shock compared with the normotensive rats. As the shock shifted to the decompensated phase, the blood flow reduction was more pronounced. BBB permeability studies using sodium fluorescein (molecular weight of 376) and Evan's Blue albumin (molecular weight of 67,000) have revealed a significant increase of the BBB permeability for sodium fluorescein in the decompensated stage of hemorrhagic shock. Western blot analysis of brain capillaries showed that the expression of the transmembrane tight junction protein occludin was reduced in response to hemorrhagic shock, and the decrease of occludin was more pronounced in the decompensated phase. A similar expression pattern was shown by the transmembrane adherens junction protein cadherin as well. Our results suggest that the decompensated phase of hemorrhagic shock is associated with disturbances of the BBB, which may be explained by the dysfunction of interendothelial junctions caused by decreased occludin and cadherin levels.
authors.affiliation: Institute of Biophysics, Biological Research Center, 6726 Szeged, Hungary. krizbai@nucleus.szbk.u-szeged.hu
authors.forename: István A
authors.initials: IA
authors.lastname: Krizbai
authors.forename: Gabor
authors.initials: G
authors.lastname: Lenzser
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Szatmari
authors.forename: Attila E
authors.initials: AE
authors.lastname: Farkas
authors.forename: Imola
authors.initials: I
authors.lastname: Wilhelm
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Fekete
authors.forename: Benedek
authors.initials: B
authors.lastname: Erdos
authors.forename: Hannelore
authors.initials: H
authors.lastname: Bauer
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Bauer
authors.forename: Peter
authors.initials: P
authors.lastname: Sandor
authors.forename: Katalin
authors.initials: K
authors.lastname: Komjati
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002199:Capillary Permeability; D002560:Cerebrovascular Circulation; D004396:Coloring Agents / Q000494:pharmacology; D005070:Evans Blue / Q000494:pharmacology; D019793:Fluorescein / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D017078:Laser-Doppler Flowmetry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D062793:Occludin; D010296:Parietal Lobe / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000473:pathology*; D013997:Time Factors; D014520:Urethane / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D004396:Coloring Agents; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D051176:beta Catenin; D014520:Urethane; D005070:Evans Blue; D019793:Fluorescein