Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression
Autor: | Karen S. Mark, Sharon Hom, Thomas P. Davis, Ken A. Witt |
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Rok vydání: | 2003 |
Předmět: |
Physiology
Butanols Blood Pressure Biology Tritium Blood–brain barrier Occludin Cell junction Tight Junctions Rats Sprague-Dawley Electrolytes Adenosine Triphosphate Physiology (medical) Laser-Doppler Flowmetry medicine Animals Claudin-3 Hypoxia Hypoxia Brain Tight junction Brain Membrane Proteins Organ Size Carbon Dioxide Hypoxia (medical) Phosphoproteins Actins Capillaries Rats Cell biology Oxygen Perfusion medicine.anatomical_structure Cerebral blood flow Blood-Brain Barrier Paracellular transport Immunology Zonula Occludens-1 Protein cardiovascular system Female medicine.symptom Cardiology and Cardiovascular Medicine |
Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 285:H2820-H2831 |
ISSN: | 1522-1539 0363-6135 |
Popis: | Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJs) that are critical for maintaining brain homeostasis. The effects of initial reoxygenation after a hypoxic insult (H/R) on functional and molecular properties of the BBB and TJs remain unclear. In situ brain perfusion and Western blot analyses were performed to assess in vivo BBB integrity on reoxygenation after a hypoxic insult of 6% O2for 1 h. Model conditions [blood pressure, blood gas chemistries, cerebral blood flow (CBF), and brain ATP concentration] were also assessed to ensure consistent levels and criteria for insult. In situ brain perfusion revealed that initial reoxygenation (10 min) significantly increased the uptake of [14C]sucrose into brain parenchyma. Capillary depletion and CBF analyses indicated the perturbations were due to increased paracellular permeability rather than vascular volume changes. Hypoxia with reoxygenation (10 min) produced an increase in BBB permeability with associated alterations in tight junctional protein expression. These results suggest that H/R leads to reorganization of TJs and increased paracellular diffusion at the BBB, which is not a result of increased CBF, vascular volume change, or endothelial uptake of marker. Additionally, the tight junctional protein occludin had a shift in bands that correlated with functional changes (i.e., increased permeability) without significant change in expression of claudin-3, zonula occludens-1, or actin. H/R-induced changes in the BBB may result in edema and/or associated pathological outcomes. |
Databáze: | OpenAIRE |
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