A novel mechanism of neuroprotection: Blood glutamate grabber

被引:75
作者
Castillo, Jose [1 ]
Isabel Loza, Maria [2 ,3 ]
Mirelman, David [4 ]
Brea, Jose [2 ,3 ]
Blanco, Miguel [1 ]
Sobrino, Tomas [1 ]
Campos, Francisco [1 ]
机构
[1] Univ Santiago de Compostela, Clin Univ Hosp, Dept Neurol, Hlth Res Inst Santiago de Compostela, Santiago De Compostela, Spain
[2] Univ Santiago de Compostela, Dept Pharmacol, Discovery Grp BioFarma, Hlth Res Inst Santiago de Compostela, Santiago De Compostela, Spain
[3] Univ Santiago de Compostela, Ctr Invest Med Mol & Enfermedades Cron CIMUS, BioFarma Res Grp, Santiago De Compostela, Spain
[4] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel
关键词
Blood-brain barrier; brain ischemia; experimental; glutamate; neuroprotection; ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; OXALOACETATE TRANSAMINASE; REPERFUSION THERAPIES; CLINICAL-TRIALS; FUTURE; RECANALIZATION; EXCITOTOXICITY; DYSFUNCTION; MODEL;
D O I
10.1177/0271678X15606721
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Glutamate excitotoxicity is a primary contributor of ischemic neuronal death and other cellular components of the neurovascular unit. Several strategies have been developed against glutamate excitotoxicity, however none of them have not shown positive results in the clinical practice so far. Nowadays, the concept of blood/brain glutamate grabbing or scavenging is well recognized as a novel and attractive protective strategy to reduce the excitotoxic effect of excess extracellular glutamate that accumulates in the brain following an ischemic stroke. The main advantage of this novel therapeutic strategy is that it occurs in the blood circulation and therefore does not affect the normal brain neurophysiology, as it has been described for other drug treatments used against glutamate excitotoxicity. In this work we report all experimental data from the beginning of our studies, focused on stroke pathology, and we describe new findings about the potential application of this therapy. Future clinical trials will allow to know the real efficacy of this novel therapeutic strategy in stroke patients.
引用
收藏
页码:292 / 301
页数:10
相关论文
共 64 条
[1]   Endovascular Therapy for Ischemic Stroke [J].
Appireddy, Ramana M. R. ;
Demchuk, Andrew M. ;
Goyal, Mayank ;
Menon, Bijoy K. ;
Eesa, Muneer ;
Choi, Philip ;
Hill, Michael D. .
JOURNAL OF CLINICAL NEUROLOGY, 2015, 11 (01) :1-8
[2]  
Asadi H, 2014, THROMBOSIS
[3]   CORM-A1 prevents blood-brain barrier dysfunction caused by ionotropic glutamate receptor-mediated endothelial oxidative stress and apoptosis [J].
Basuroy, Shyamali ;
Leffler, Charles W. ;
Parfenova, Helena .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2013, 304 (11) :C1105-C1115
[4]   Pyruvate's blood glutamate scavenging activity contributes to the spectrum of its neuroprotective mechanisms in a rat model of stroke [J].
Boyko, Matthew ;
Zlotnik, Alexander ;
Gruenbaum, Benjamin F. ;
Gruenbaum, Shaun E. ;
Ohayon, Sharon ;
Kuts, Ruslan ;
Melamed, Israel ;
Regev, Adi ;
Shapira, Yoram ;
Teichberg, Vivian I. .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2011, 34 (09) :1432-1441
[5]   Oxaloacetate: A novel neuroprotective for acute ischemic stroke [J].
Campos, Francisco ;
Sobrino, Tomas ;
Ramos-Cabrer, Pedro ;
Castillo, Jose .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2012, 44 (02) :262-265
[6]   Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: an experimental study [J].
Campos, Francisco ;
Sobrino, Tomas ;
Ramos-Cabrer, Pedro ;
Argibay, Barbara ;
Agulla, Jesus ;
Perez-Mato, Maria ;
Rodriguez-Gonzalez, Raquel ;
Brea, David ;
Castillo, Jose .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2011, 31 (06) :1378-1386
[7]   High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke [J].
Campos, Francisco ;
Sobrino, Tomas ;
Ramos-Cabrer, Pedro ;
Castellanos, Mar ;
Blanco, Miguel ;
Rodriguez-Yanez, Manuel ;
Serena, Joaquin ;
Leira, Rogelio ;
Castillo, Jose .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2011, 31 (06) :1387-1393
[8]   Blood levels of glutamate oxaloacetate transaminase are more strongly associated with good outcome in acute ischaemic stroke than glutamate pyruvate transaminase levels [J].
Campos, Francisco ;
Rodriguez-Yanez, Manuel ;
Castellanos, Mar ;
Arias, Susana ;
Perez-Mato, Maria ;
Sobrino, Tomas ;
Blanco, Miguel ;
Serena, Joaquin ;
Castillo, Jose .
CLINICAL SCIENCE, 2011, 121 (1-2) :11-17
[9]   Aggravation of acute ischemic stroke by hyperthermia is related to an excitotoxic mechanism [J].
Castillo, J ;
Dávalos, A ;
Noya, M .
CEREBROVASCULAR DISEASES, 1999, 9 (01) :22-27
[10]   Progression of ischaemic stroke and excitotoxic aminoacids [J].
Castillo, J ;
Davalos, A ;
Noya, M .
LANCET, 1997, 349 (9045) :79-83