Therapeutic effect of tPA in ischemic stroke is enhanced by its combination with normobaric oxygen and hypothermia or ethanol

Brain Research
Zhili JiYuchuan Ding

Abstract

Our lab has previously elucidated the neuroprotective effects of normobaric oxygen (NBO) and ethanol (EtOH) in ischemic stroke. The present study further evaluated the effect of EtOH or hypothermia (Hypo) in the presence of low concentration of NBO and determined whether EtOH can substitute hypothermia in a more clinically relevant autologous embolus rat stroke model in which reperfusion was established by tissue-type plasminogen activator (t-PA). At 1h of middle cerebral artery occlusion (MCAO) by an autologous embolus, rats received t-PA. In addition, at the same time, ischemic animals were treated with either EtOH (1.0 g/kg) or hypothermia (33°C for 3h) in combination with NBO (60% for 3h). Extent of neuroprotection was assessed by apoptotic cell death measured by ELISA and Western immunoblotting analysis for pro- (AIF, activated Caspase-3, Bax) and anti-apoptotic (Bcl-2) protein expression at 3 and 24h of reperfusion induced by t-PA administration. Compared to ischemic rats treated only with t-PA, animals with NBO, hypothermia or EtOH had significantly reduced apoptotic cell death by 32.5%, 43.1% and 36.0% respectively. Furthermore, combination therapy that included NBO+EtOH or NBO+Hypo with t-PA exhibited a much larger dec...Continue Reading

References

Aug 1, 1995·Stroke; a Journal of Cerebral Circulation·N NighoghossianF Salord
Jan 1, 1997·Neuroscience and Biobehavioral Reviews·F C BaroneR F White
Dec 4, 1998·Stroke; a Journal of Cerebral Circulation·S SchwabW Hacke
Aug 13, 1999·Genes & Development·A GrossS J Korsmeyer
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·A M Chinnaiyan
Sep 8, 2001·Stroke; a Journal of Cerebral Circulation·S SchwabS A Mayer
Feb 8, 2003·Stroke; a Journal of Cerebral Circulation·Daniel E RusyniakUNKNOWN Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study
May 29, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Maria ErecinskaIan A Silver
Aug 28, 2003·Lancet Neurology·Valery FeiginCraig Anderson
Apr 23, 2004·The EMBO Journal·Michelle M HillSeamus J Martin
Feb 9, 2005·Critical Care Medicine·Michael HolzerUNKNOWN Collaborative Group on Induced Hypothermia for Neuroprotection After Cardiac Arrest
Nov 28, 2006·Frontiers in Bioscience : a Journal and Virtual Library·Liping Liu, Midori A Yenari
Apr 19, 2007·Neurological Research·John W CalvertJohn H Zhang
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Jan 22, 2008·Hearing Research·Weidong QiRichard J Salvi
Jun 26, 2009·Critical Care Medicine·Kees H Polderman
Apr 13, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Zuo-Hui ShaoTerry L Vanden Hoek
Apr 29, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Li SunRoland Veltkamp
Sep 22, 2010·Annual Review of Medicine·Joshua W Lampe, Lance B Becker
Nov 5, 2011·Stroke; a Journal of Cerebral Circulation·Fei WangYuchuan Ding
Jan 11, 2012·Archives of Internal Medicine·Alexander D CornetYvo M Smulders
Feb 2, 2012·Current Treatment Options in Neurology·Rainer Kollmar, Stefan Schwab
Mar 9, 2013·CNS & Neurological Disorders Drug Targets·Meijuan ZhangFeng Zhang
Mar 21, 2013·Neuroscience Research·Paul FuYuchuan Ding
Mar 21, 2013·Stroke; a Journal of Cerebral Circulation·Xiaokun GengYuchuan Ding
Dec 7, 2013·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Zhijuan CaoSean P Marrelli
Mar 6, 2015·Nature Protocols·Li ZhangZheng Gang Zhang

❮ Previous
Next ❯

Citations

Jan 24, 2017·The International Journal of Neuroscience·Hongxing ZhouSheng Tan
Feb 22, 2017·Medical Gas Research·Wen-Cao Liu, Xin-Chun Jin
Feb 23, 2020·Frontiers in Neurology·Zhiying ChenRan Meng
Dec 4, 2020·Neural Regeneration Research·Zhe ChengYu-Chuan Ding
Jul 27, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Meng WangYuchuan Ding

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.