A combination antioxidant therapy to inhibit NOX2 and activate Nrf2 decreases secondary brain damage and improves functional recovery after traumatic brain injury

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Raghavendar ChandranRaghu Vemuganti

Abstract

Uncontrolled oxidative stress contributes to the secondary neuronal death that promotes long-term neurological dysfunction following traumatic brain injury (TBI). Surprisingly, both NADPH oxidase 2 (NOX2) that increases and transcription factor Nrf2 that decreases reactive oxygen species (ROS) are induced after TBI. As the post-injury functional outcome depends on the balance of these opposing molecular pathways, we evaluated the effect of TBI on the motor and cognitive deficits and cortical contusion volume in NOX2 and Nrf2 knockout mice. Genetic deletion of NOX2 improved, while Nrf2 worsened the post-TBI motor function recovery and lesion volume indicating that decreasing ROS levels might be beneficial after TBI. Treatment with either apocynin (NOX2 inhibitor) or TBHQ (Nrf2 activator) alone significantly improved the motor function after TBI, but had no effect on the lesion volume, compared to vehicle control. Whereas, the combo therapy (apocynin + TBHQ) given at either 5 min/24 h or 2 h/24 h improved motor and cognitive function and decreased cortical contusion volume compared to vehicle group. Thus, both the generation and disposal of ROS are important modulators of oxidative stress, and a combo therapy that prevents ROS fo...Continue Reading

References

Oct 8, 2004·Journal of Biochemistry and Molecular Biology·Jong-Min Lee, Jeffrey A Johnson
Nov 3, 2004·Trends in Molecular Medicine·Hozumi Motohashi, Masayuki Yamamoto
Nov 4, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andy Y ShihTimothy H Murphy
Sep 14, 2006·Annual Review of Pharmacology and Toxicology·Thomas W KenslerShyam Biswal
Dec 28, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yi-Ping YanRobert J Dempsey
Jan 24, 2007·Physiological Reviews·Karen Bedard, Karl-Heinz Krause
Oct 27, 2007·Stroke; a Journal of Cerebral Circulation·Xiurong ZhaoJaroslaw Aronowski
Nov 6, 2007·Antioxidants & Redox Signaling·Jyoti D Malhotra, Randal J Kaufman
Dec 29, 2007·Neuroscience Letters·Wei YanHong-Xia Yin
May 10, 2008·Arteriosclerosis, Thrombosis, and Vascular Biology·Narayana AnilkumarAjay M Shah
Aug 5, 2008·Free Radical Biology & Medicine·Angélica CoyoyJulio Morán
Aug 23, 2008·Antioxidants & Redox Signaling·Marcus J CalkinsJeffrey A Johnson
Dec 20, 2008·Mediators of Inflammation·J Stefanska, R Pawliczak
May 7, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hai ChenPak H Chan
Jun 9, 2009·Nature Neuroscience·Angela M BrennanRaymond A Swanson
Jun 12, 2009·Neuroscience Letters·Pramod K DashAnthony N Moore
Jun 18, 2009·Expert Opinion on Therapeutic Targets·Jinqing LiTaixing Cui
Jun 26, 2009·Nature Neuroscience·Nicolas Demaurex, Luca Scorrano
Dec 10, 2009·Molecular and Cellular Biology·Katharina von LöhneysenUlla G Knaus
Feb 5, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Edward D HallAyman G Mustafa
Feb 13, 2010·Expert Opinion on Therapeutic Targets·A BouttenM Bonay
Jul 28, 2010·Journal of Neuroinflammation·Kenji DohiTohru Aruga
Aug 18, 2010·Antioxidants & Redox Signaling·Pelin CengizDandan Sun
Dec 9, 2010·Brain Research·Tiziana GenoveseSalvatore Cuzzocrea
Jan 26, 2011·Molecular and Cellular Neurosciences·Kazutoshi MurotomiKouichi Tanonaka
Dec 29, 2011·Journal of Neurotrauma·Haris HaticBruce A Citron
Oct 3, 2012·Progress in Neurobiology·Meijuan ZhangFeng Zhang
Feb 28, 2013·Nature Reviews. Neurology·Bob RoozenbeekDavid K Menon
Apr 4, 2013·Antioxidants & Redox Signaling·Carolin CorneliusSalvatore Cuzzocrea
Dec 20, 2013·Current Medicinal Chemistry·Ana Rodríguez-RodríguezAntonio Carrillo-Vico
Feb 12, 2014·Antioxidants & Redox Signaling·Becky A DieboldJ David Lambeth

❮ Previous
Next ❯

Citations

Nov 23, 2017·International Journal of Molecular Sciences·Dong-Hee Choi, Jongmin Lee
Jan 23, 2020·ASN Neuro·Mikah S Brandes, Nora E Gray
Mar 9, 2019·Cellular & Molecular Immunology·Kaibin ShiFu-Dong Shi
Jan 31, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Neel S SinghalDengke K Ma
Apr 19, 2019·Journal of Neuroinflammation·Diego Rolando Hernández-EspinosaJulio Morán
Dec 13, 2018·Science Signaling·TaeHee KimRaghu Vemuganti
Jan 25, 2021·Neuromolecular Medicine·Raghavendar ChandranRaghu Vemuganti
Jul 11, 2019·Recent Patents on Food, Nutrition & Agriculture·Tahereh FarkhondehLeila Peivasteh-Roudsari
Aug 16, 2019·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Edward J CalabreseRehana K Leak
May 7, 2020·Free Radical Biology & Medicine·Aslihan Terzi, Daniel M Suter
Apr 4, 2021·International Journal of Molecular Sciences·Chiara MelePaolo Marzullo

❮ Previous
Next ❯

Methods Mentioned

BETA
gene knockouts
ubiquitination

Software Mentioned

GraphPad Prism
ImageJ
NIH ImageJ
ARRIVE

Related Concepts

Related Feeds

Brain Injury & Trauma

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