Blood-Brain Barrier Permeability Is Exacerbated in Experimental Model of Hepatic Encephalopathy via MMP-9 Activation and Downregulation of Tight Junction Proteins

Molecular Neurobiology
Saurabh Dhanda, Rajat Sandhir

Abstract

The present study was designed to investigate the mechanisms involved in blood-brain barrier (BBB) permeability in bile duct ligation (BDL) model of chronic hepatic encephalopathy (HE). Four weeks after BDL surgery, a significant increase was observed in serum bilirubin levels. Masson trichrome staining revealed severe hepatic fibrosis in the BDL rats. 99mTc-mebrofenin retention was increased in the liver of BDL rats suggesting impaired hepatobiliary transport. An increase in permeability to sodium fluorescein, Evans blue, and fluorescein isothiocyanate (FITC)-dextran along with increase in water and electrolyte content was observed in brain regions of BDL rats suggesting disrupted BBB. Increased brain water content can be attributed to increase in aquaporin-4 mRNA and protein expression in BDL rats. Matrix metalloproteinase-9 (MMP-9) mRNA and protein expression was increased in brain regions of BDL rats. Additionally, mRNA and protein expression of tissue inhibitor of matrix metalloproteinases (TIMPs) was also increased in different regions of brain. A significant decrease in mRNA expression and protein levels of tight junction proteins, viz., occludin, claudin-5, and zona occluden-1 (ZO-1) was observed in different brain regi...Continue Reading

References

Mar 1, 1991·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A H LockwoodW H Wong
Dec 1, 1988·Journal of Neuro-oncology·D E Weissman, C Stewart
Feb 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·B F Trump, I K Berezesky
Jan 1, 1994·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A L BetzX D Ren
Oct 1, 1995·Journal of Neurotrauma·G A Rosenberg
Nov 17, 1999·Proceedings of the Society for Experimental Biology and Medicine·A S Hazell, R F Butterworth
Dec 12, 2001·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Y GascheP H Chan
Nov 7, 2003·Neurochemistry International·Peter Ott, Fin Stolze Larsen
Dec 10, 2003·Neuroreport·K V Rama RaoM D Norenberg
Nov 24, 2004·Metabolic Brain Disease·M D NorenbergK V Rama Rao
Apr 2, 2005·The Journal of Biological Chemistry·Christopher RoseHelmut Kettenmann
May 26, 2005·Pharmacological Reviews·Brian T Hawkins, Thomas P Davis
Mar 25, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ravindra A KalePonnada A Narayana
May 3, 2006·The American Journal of Pathology·Jing-Lin XiaYouhua Liu
May 5, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·A R JayakumarM D Norenberg
May 27, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rodrigo JoverMiguel Pérez-Mateo
Jul 20, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yi YangGary A Rosenberg
May 25, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gavin WrightRajiv Jalan
Jul 25, 2007·Seminars in Cell & Developmental Biology·Smriti M AgrawalV Wee Yong
Jan 16, 2008·The British Journal of Surgery·P GeorgievP-A Clavien
Jun 24, 2008·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Naoki ShimojimaJustin H Nguyen
Aug 2, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Giuseppe CalamitaMaria Svelto
Oct 14, 2008·The Journal of Biological Chemistry·Arumugam R JayakumarMichael D Norenberg
May 12, 2009·Neurochemistry International·Kei SawaraRoger F Butterworth
Jul 30, 2009·Liver International : Official Journal of the International Association for the Study of the Liver·Roger F ButterworthUNKNOWN Members of the ISHEN Commission on Experimental Models of HE
Aug 12, 2009·Neurobiology of Disease·N Joan AbbottDavid J Begley
Oct 13, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Feng ChenJustin H Nguyen
Nov 6, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Debbie L ShawcrossRobin D Hughes
Jan 19, 2010·Cell Calcium·Maiken Nedergaard, Alexei Verkhratsky
Feb 23, 2010·Brain Research·Konstantinos FaropoulosDimitris Konstantinou
May 11, 2010·Journal of Hepatology·Gavin WrightRajiv Jalan
May 25, 2010·Liver International : Official Journal of the International Association for the Study of the Liver·Sa LvPei Liu

❮ Previous
Next ❯

Citations

Oct 14, 2017·F1000Research·Victoria LiereSharon DeMorrow
Dec 13, 2019·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Yating JianGuilian Zhang
Nov 16, 2017·Metabolic Brain Disease·Saurabh DhandaRajat Sandhir
Nov 27, 2019·Biomicrofluidics·Pedram MotallebnejadSamira M Azarin
Jan 21, 2021·International Journal of Molecular Sciences·So Yeong Cheon, Juhyun Song
Feb 9, 2021·Frontiers in Cellular and Infection Microbiology·Zefeng ChenGuobin Wu
May 25, 2021·Archives of Pharmacal Research·Ajay UpretySoo Young Kim

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
electrophoresis
PCR
zymography

Software Mentioned

LightCycler
ImageJ

Related Concepts

Related Feeds

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.