Blood glutamate grabbing does not reduce the hematoma in an intracerebral hemorrhage model but it is a safe excitotoxic treatment modality

被引:21
作者
da Silva-Candal, Andres [1 ]
Vieites-Prado, Alba [1 ]
Gutierrez-Fernandez, Maria [2 ,3 ]
Rey, Ramon I. [1 ]
Argibay, Barbara [1 ]
Mirelman, David [4 ]
Sobrino, Tomas [1 ]
Rodriguez-Frutos, Berta [2 ,3 ]
Castillo, Jose [1 ]
Campos, Francisco [1 ]
机构
[1] Univ Santiago de Compostela, Hlth Res Inst Santiago de Compostela IDIS, Clin Neurosci Res Lab, Dept Neurol,Hosp Clin Univ, Santiago De Compostela, Spain
[2] Univ Autonoma Madrid, Dept Neurol, Neurosci & Cerebrovasc Res Lab, Madrid, Spain
[3] Univ Autonoma Madrid, La Paz Univ Hosp, IdiPAZ Hlth Res Inst, Stroke Ctr,Neurosci Area, Madrid, Spain
[4] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel
关键词
blood glutamate grabbing; GOT; intracerebral hemorrhage; oxaloacetate; protection; OXALOACETATE TRANSAMINASE; SCAVENGERS OXALOACETATE; CEREBRAL-ISCHEMIA; BRAIN-INJURY; MEMANTINE; PYRUVATE; STROKE; NEUROPROTECTION; MECHANISMS; THERAPIES;
D O I
10.1038/jcbfm.2015.28
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Recent studies have shown that blood glutamate grabbing is an effective strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. The purpose of the study was to investigate the effect of two of the most efficient blood glutamate grabbers (oxaloacetate and recombinant glutamate oxaloacetate transaminase 1: rGOT1) in a rat model of intracerebral hemorrhage (ICH). Intracerebral hemorrhage was produced by injecting collagenase into the basal ganglia. Three treatment groups were developed: a control group treated with saline, a group treated with oxaloacetate, and a final group treated with human rGOT1. Treatments were given 1 hour after hemorrhage. Hematoma volume (analyzed by magnetic resonance imaging (MRI)), neurologic deficit, and blood glutamate and GOT levels were quantified over a period of 14 days after surgery. The results observed showed that the treatments used induced a significant reduction of blood glutamate levels; however, they did not reduce the hematoma, nor did they improve the neurologic deficit. In the present experimental study, we have shown that this novel therapeutic strategy is not effective in case of ICH pathology. More importantly, these findings suggest that blood glutamate grabbers are a safe treatment modality that can be given in cases of suspected ischemic stroke without previous neuroimaging.
引用
收藏
页码:1206 / 1212
页数:7
相关论文
共 36 条
[1]   Complications of intracerebral haemorrhage [J].
Balami, Joyce S. ;
Buchan, Alastair M. .
LANCET NEUROLOGY, 2012, 11 (01) :101-118
[2]   Emerging experimental therapies for intracerebral hemorrhage: targeting mechanisms of secondary brain injury [J].
Belur, Praveen K. ;
Chang, Jason J. ;
He, Shuhan ;
Emanuel, Benjamin A. ;
Mack, William J. .
NEUROSURGICAL FOCUS, 2013, 34 (05)
[3]   Brain to blood glutamate scavenging as a novel therapeutic modality: a review [J].
Boyko, Matthew ;
Gruenbaum, Shaun E. ;
Gruenbaum, Benjamin F. ;
Shapira, Yoram ;
Zlotnik, Alexander .
JOURNAL OF NEURAL TRANSMISSION, 2014, 121 (08) :971-979
[4]   The Effect of Blood Glutamate Scavengers Oxaloacetate and Pyruvate on Neurological Outcome in a Rat Model of Subarachnoid Hemorrhage [J].
Boyko, Matthew ;
Melamed, Israel ;
Gruenbaum, Benjamin Fredrick ;
Gruenbaum, Shaun Evan ;
Ohayon, Sharon ;
Leibowitz, Akiva ;
Brotfain, Evgeny ;
Shapira, Yoram ;
Zlotnik, Alexander .
NEUROTHERAPEUTICS, 2012, 9 (03) :649-657
[5]   Pharmacokinetics of Glutamate-Oxaloacetate Transaminase and Glutamate-Pyruvate Transaminase and Their Blood Glutamate-Lowering Activity in Naive Rats [J].
Boyko, Matthew ;
Stepensky, David ;
Gruenbaum, Benjamin F. ;
Gruenbaum, Shaun E. ;
Melamed, Israel ;
Ohayon, Sharon ;
Glazer, Michael ;
Shapira, Yoram ;
Zlotnik, Alexander .
NEUROCHEMICAL RESEARCH, 2012, 37 (10) :2198-2205
[6]   Hyperthermia in Human Ischemic and Hemorrhagic Stroke: Similar Outcome, Different Mechanisms [J].
Campos, Francisco ;
Sobrino, Tomas ;
Vieites-Prado, Alba ;
Perez-Mato, Maria ;
Rodriguez-Yanez, Manuel ;
Blanco, Miguel ;
Castillo, Jose .
PLOS ONE, 2013, 8 (11)
[7]   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
[8]   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
[9]   Molecular signatures of brain injury after intracerebral hemorrhage [J].
Castillo, J ;
Dávalos, A ;
Alvarez-Sabín, J ;
Pumar, JM ;
Leira, R ;
Silva, Y ;
Montaner, J ;
Kase, CS .
NEUROLOGY, 2002, 58 (04) :624-629
[10]   Immunotherapy blocking the tissue plasminogen activator-dependent activation of N-methyl-D-aspartate glutamate receptors improves hemorrhagic stroke outcome [J].
Gaberel, Thomas ;
Macrez, Richard ;
Gauberti, Maxime ;
Montagne, Axel ;
Hebert, Marie ;
Petersen, Karl-Uwe ;
Touze, Emmanuel ;
Agin, Veronique ;
Emery, Evelyne ;
Ali, Carine ;
Vivien, Denis .
NEUROPHARMACOLOGY, 2013, 67 :267-271