Effects of Lipopolysaccharide on the Blood-Brain Barrier Permeability in Prolonged Nitric Oxide Blockade-Induced Hypertensive Rats

• Published in: International journal of neuroscience 2005-02, Vol.115 (2), p.151-168
• Main Authors: AHISHALI, B., KAYA, M., KALAYCI, R., UZUN, H., BILGIC, B., ARICAN, N., ELMAS, I., AYDIN, S., KUCUK, M.
• Format: Article
• Language: English
• Subjects: Angiotensin II - metabolism; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Animals; Astrocytes - drug effects; Astrocytes - pathology; Biological and medical sciences; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Capillary Permeability - drug effects; Cerebellum - drug effects; Cerebellum - metabolism; Cerebellum - pathology; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Coloring Agents - pharmacokinetics; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - adverse effects; Enzyme-Linked Immunosorbent Assay; Evans Blue - pharmacokinetics; Evans blue extravasation; Extravasation of Diagnostic and Therapeutic Materials; Fundamental and applied biological sciences. Psychology; glial fibrillary acidic protein; Hypertension - chemically induced; Hypertension - drug therapy; Interleukin-1 - blood; Interleukin-6 - blood; L-NAME; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - pharmacology; LPS; Male; Membrane Proteins - drug effects; NG-Nitroarginine Methyl Ester - administration & dosage; NG-Nitroarginine Methyl Ester - adverse effects; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - metabolism; occludin; Phosphoproteins - drug effects; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha - metabolism; Vertebrates: nervous system and sense organs; zonula occludens-1; Zonula Occludens-1 Protein
• ISSN: 0020-7454; 1563-5279; 1543-5245
• DOI: 10.1080/00207450590519030

The authors investigated the effects of lipopolysaccharide (LPS) on the blood-brain barrier (BBB) integrity and the activity of astrocytes during the Nw-nitro-L-arginine methyl ester (L-NAME) hypertension followed by angiotensin (ANG) II in rats. They measured the changes in the BBB permeability using the Evans blue (EB) dye and concomitantly in the levels of TNF-a, IL-1b, and IL-6 in serum and nitric oxide in plasma. The authors performed two tight junction-specific proteins, zonula occludens-1 and occludin, and glial fibrillary acidic protein, by using immunohisto-chemical method. The serum levels of TNF-α, IL-1β, IL-6, and the plasma level of nitric oxide significantly increased in LPS-treated rats (p < .01). The EB dye extravasation increased in cerebellum (p < .001) and diencephalon (p < .05) of L-NAME plus ANG II-treated animals. However, LPS reduced the increased EB dye extravasation in the brain regions of L-NAME-induced hypertensive rats treated with ANG II (p < .001). In L-NAME, there was a considerable loss of staining in both zonula occludens-1 and occludin. Staining for zonula occludens-1 and occludin was highly intensive in animals treated with LPS. Glial fibrillary acidic protein staining was seen in a few astrocytes in brains of L-NAME-treated animals. However, this staining showed an increased intensity in the brain sections of animals treated with LPS. This study indicates that, in L-NAME hypertensive rats, ANG II leads to an increase in the extravasation of EB dye to brain as a result of decreased activity of tight junction proteins and astrocytes, and LPS could significantly attenuate the EB dye transport to the brain through the increased activity of tight junction proteins and astrocytes.