Effects of lipopolysaccharide on the blood-brain barrier permeability in prolonged nitric oxide blockade-induced hypertensive rats.
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-a, IL-1 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.
Ahishali
B
B
Department of Histology and Embryology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Kaya
M
M
Kalayci
R
R
Uzun
H
H
Bilgic
B
B
Arican
N
N
Elmas
I
I
Aydin
S
S
Kucuk
M
M
D000804:Angiotensin II / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004396:Coloring Agents / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D005070:Evans Blue / Q000493:pharmacokinetics; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000009:adverse effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010750:Phosphoproteins / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D000806:Angiotensin-Converting Enzyme Inhibitors; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010750:Phosphoproteins; C569044:Tjp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D000804:Angiotensin II; D009569:Nitric Oxide; D005070:Evans Blue; D019331:NG-Nitroarginine Methyl Ester