Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Christopher D HueBarclay Morrison

Abstract

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α(+) isof...Continue Reading

References

Sep 1, 1992·Cleveland Clinic Journal of Medicine·D Walsh, J Avashia
May 1, 1992·The American Journal of Physiology·E WillottJ M Anderson
Jun 1, 1992·Journal of Neurology, Neurosurgery, and Psychiatry·D H MillerW I McDonald
Jun 1, 1991·Current Opinion in Rheumatology·R P Kimberly
Apr 1, 1993·The American Journal of Physiology·M S Balda, J M Anderson
Aug 13, 1999·The American Journal of Physiology·J L UnderwoodJ A Alvarado
Nov 21, 2002·Pharmacology & Therapeutics·Heike SchäckeKhusru Asadullah
Nov 14, 2003·American Journal of Physiology. Cell Physiology·Jorge A AlvaradoLorenza González-Mariscal
Dec 20, 2003·Stroke; a Journal of Cerebral Circulation·Niphon Poungvarin
Jan 1, 2005·Current Opinion in Oncology·Evert C A Kaal, Charles J Vecht
Oct 21, 2005·The New England Journal of Medicine·Turk Rhen, John A Cidlowski
Mar 18, 2006·The Journal of Physiology·Carola FörsterDetlev Drenckhahn
Sep 20, 2006·The Journal of Head Trauma Rehabilitation·Deborah Warden
Feb 1, 2008·The New England Journal of Medicine·Charles W HogeCarl A Castro
Aug 12, 2009·Neurobiology of Disease·N Joan AbbottDavid J Begley
Jun 17, 2010·Nature Reviews. Neurology·Dan ShlosbergAlon Friedman
Apr 1, 2011·Journal of Neurotrauma·Robert H GarmanPatrick M Kochanek
Mar 28, 2013·The Journal of Endocrinology·Michela CampoloSalvatore Cuzzocrea
Apr 10, 2013·Annals of Biomedical Engineering·Stewart YeohKenneth L Monson
Apr 16, 2013·Journal of Neurotrauma·Christopher D HueBarclay Morrison

❮ Previous
Next ❯

Citations

Aug 23, 2016·Current Pathobiology Reports·Ellaine SalvadorCarola Y Förster
Jul 21, 2017·Journal of Neurotrauma·Thomas W SawyerLori McLaws
Oct 31, 2019·Brain : a Journal of Neurology·Cameron J HertingDolores Hambardzumyan
Jul 11, 2019·Current Treatment Options in Neurology·Nicholas A Vitanza, Michelle Monje
Jan 13, 2018·Expert Review of Neurotherapeutics·Nicole A P LiebermanCourtney A Crane
Mar 25, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Wonho NaBong-Gun Ju
May 12, 2020·Frontiers in Endocrinology·Gianfranco Umberto Meduri, George P Chrousos
Sep 29, 2015·Journal of Neurotrauma·Christopher D HueBarclay Morrison Iii
May 10, 2019·Frontiers in Neurology·Zoe M TappOlga N Kokiko-Cochran
Feb 11, 2020·Fluids and Barriers of the CNS·Lilla BarnaMária A Deli
Mar 3, 2020·Frontiers in Aging Neuroscience·Patrizia GiannoniNicola Marchi
Apr 16, 2019·Frontiers in Molecular Neuroscience·Marta CenciariniMauro Pessia
Jul 8, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Alejandro EspinosaEdda Sciutto
Sep 15, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Min ShenYuan-Lin Zheng
Mar 4, 2021·Surgical Neurology International·G Lakshmi Prasad
Feb 23, 2021·Toxicon : Official Journal of the International Society on Toxinology·Bunyamin TrasKamil Uney
Mar 7, 2021·International Journal of Molecular Sciences·Luis O Soto-RojasJosé Luna-Muñoz
Apr 8, 2021·Fluids and Barriers of the CNS·Stephanie A IheziePeeyush Kumar Thankamani Pandit
May 7, 2021·Journal of Cellular and Molecular Medicine·Jian ShenJianwei Pan
Aug 8, 2021·International Journal of Molecular Sciences·Elena Rybnikova, Natalia Nalivaeva
Oct 13, 2021·Cellular and Molecular Neurobiology·Shusheng WuLongfei Du

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis

Software Mentioned

MetaMorph
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.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.