The effects of hyperbaric oxygen therapy on blood–brain barrier permeability in septic rats

Abstract The mechanisms underlying the changes in blood–brain barrier (BBB) integrity in septic encephalopathy are poorly understood. The present study was designed to examine whether hyperbaric oxygen therapy (HBOT) influences the response of BBB to sepsis induced by cecal ligation and puncture (CL...

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Published in:	Brain research Vol. 1412; pp. 63 - 72
Main Authors:	Avtan, Sezen Milli, Kaya, Mehmet, Orhan, Nurcan, Arslan, Abdullah, Arican, Nadir, Toklu, Akin Savas, Gürses, Candan, Elmas, Imdat, Kucuk, Mutlu, Ahishali, Bulent
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 15-09-2011 Elsevier
Subjects:	Animals Biological and medical sciences Blood Pressure - physiology Blood-Brain Barrier - metabolism Blood–brain barrier brain Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Cerebral Cortex - metabolism encephalopathy endothelial cells Evans blue Female Fundamental and applied biological sciences. Psychology glutathione Glutathione - metabolism Hippocampus - metabolism Horseradish peroxidase Hyperbaric oxygen therapy Hyperbaric Oxygenation immunohistochemistry malondialdehyde Malondialdehyde - metabolism Neurology occludins oxygen Permeability peroxidase protective effect Rats Rats, Wistar Sepsis Sepsis - metabolism Sepsis - therapy therapeutics tracer techniques tumor necrosis factor-alpha Tumor Necrosis Factor-alpha - metabolism Vertebrates: nervous system and sense organs Western blotting MABP BBB CLP glutathione HRP MDA phosphate-buffered saline tumor necrosis factor-alpha SE blood–brain barrier septic encephalopathy horseradish peroxidase reactive oxygen species malondialdehyde GSH EB tight junction PBS Evans blue TBS hydrogen peroxide SOD H 2O 2 TNF-α TJ superoxide dismutase ROS mean arterial blood pressure hyperbaric oxygen therapy tris-buffered saline Sepsis HBOT cecal ligation and puncture Hyperbaric oxygen therapy Horseradish peroxidase Blood–brain barrier Rat Enzyme Rodentia Central nervous system Hyperbaric oxygen Permeability Blood brain barrier Encephalon Infection Vertebrata Mammalia Treatment Peroxidases Blood-brain barrier Animal Peroxidase Oxidoreductases
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Summary:	Abstract The mechanisms underlying the changes in blood–brain barrier (BBB) integrity in septic encephalopathy are poorly understood. The present study was designed to examine whether hyperbaric oxygen therapy (HBOT) influences the response of BBB to sepsis induced by cecal ligation and puncture (CLP) in rats. Cerebral cortical and hippocampal tissue levels of tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA) and glutathione (GSH) levels were measured. BBB permeability was functionally and structurally evaluated by determining extravasation of Evans blue (EB) and horseradish peroxidase (HRP) tracers, respectively. Immunohistochemistry and western blotting for occludin were performed. HBOT did not alter TNF-α levels in CLP operated rats while a significant decrease was noted when the therapy was subjected to intact rats. MDA levels in animals subjected to CLP plus HBOT were significantly decreased. In septic rats, the decreased GSH levels were significantly increased by HBOT. While HBOT attenuated the increased BBB permeability to EB in rats subjected to CLP (P < 0.01), no macroscopic alteration was observed in the enhanced HRP extravasation. An increase in HRP extravasation was also observed by HBOT in intact animals. Occludin immunoreactivity and expression remained essentially unchanged in the brain capillaries of animals in all groups. Ultrastructurally, frequent vesicles containing HRP reaction products were observed in brain capillary endothelial cells of animals treated with CLP and/or HBOT. In conclusion, our results revealed that HBOT did not provide overall protective effects on the BBB integrity in septic conditions and even led to BBB disruption in intact animals.
Bibliography:	http://dx.doi.org/10.1016/j.brainres.2011.07.020 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0006-8993 1872-6240
DOI:	10.1016/j.brainres.2011.07.020