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Uremia induces upregulation of cerebral tissue oxidative/inflammatory cascade, down-regulation of Nrf2 pathway and disruption of blood brain barrier.

Abstract：

:Chronic kidney disease (CKD) results in various central nervous systems (CNS) disorders including cognitive dysfunction, depression, anxiety, movement disorders, seizures and encephalopathy. Uremic retention products, oxidative stress, inflammation and impaired blood-brain barrier have been implicated as the major mediators of CKD-induced CNS disorders. However, mechanisms of CKD-induced cerebral tissue oxidative stress, inflammation and impaired blood brain barrier have not been fully elucidated and were explored. Male Sprague Dawley rats underwent sham operation or 5/6 nephrectomy and were observed for 10 weeks. Arterial pressure, body weight, and renal function were monitored. Under general anesthesia the animals' cerebral cortex was harvested. Nuclear translocations of NF-κB and Nrf2 and their key target gene products, neuronal, endothelial and inducible NO synthase (NOS) isoforms, markers of oxidative, nitrosative and myeloperoxidase reactions, fibrosis mediators and key protein constituents of capillary endothelial junctional complex were determined by Western blot analysis. The CKD rats exhibited reduced body weight, hypertension, elevated serum urea and creatinine concentrations. Compared to control group cerebral cortex of the CKD group showed activation (increased nuclear translocation) of NF-κB, elevation of pro-oxidant and pro-inflammatory molecules, diminished nuclear translocation of Nrf2 and expression of cytoprotective antioxidant molecules and depletion of the key protein constituents of endothelial junctional complex. In conclusion CKD results in the cerebral tissue activation of inflammatory and oxidative pathways, inhibition of antioxidant and cytoprotective system and erosion of cerebral capillary junctional complex, events that contribute to CNS dysfunction and impaired blood brain barrier.

journal_name

Am J Transl Res

journal_title

American journal of translational research

authors

Jing W,Jabbari B,Vaziri ND

subject

Has Abstract

pub_date

2018-07-15 00:00:00

pages

2137-2147

issue

issn

1943-8141

journal_volume

pub_type

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Uremia induces upregulation of cerebral tissue oxidative/inflammatory cascade, down-regulation of Nrf2 pathway and disruption of blood brain barrier.