title: Pyruvate's blood glutamate scavenging activity contributes to the spectrum of its neuroprotective mechanisms in a rat model of stroke.
abstract: In previous studies, we have shown that by increasing the brain-to-blood glutamate efflux upon scavenging blood glutamate with either oxaloacetate or pyruvate, one achieves highly significant neuroprotection particularly in the context of traumatic brain injury. The current study examines, for the first time, how the blood glutamate scavenging properties of glutamate-pyruvate transaminase (GPT), alone or in combination with pyruvate, may contribute to the spectrum of its neuroprotective mechanisms and improve the outcome of rats exposed to brain ischemia, as they do after head trauma. Rats that were exposed to permanent middle cerebral artery occlusion (MCAO) and treated with intravenous 250 mg/kg pyruvate had a smaller volume of infarction and reduced brain edema, resulting in an improved neurological outcome and reduced mortality compared to control rats treated with saline. Intravenous pyruvate at the low dose of 31.3 mg/kg did not demonstrate any neuroprotection. However, when combined with 0.6 mg/kg of GPT there was a similar neuroprotection observed as seen with pyruvate at 250 mg/kg. Animals treated with 1.69 g/kg glutamate had a worse neurological outcome and a larger extent of brain edema. The decrease in mortality, infarcted brain volume and edema, as well as the improved neurological outcome following MCAO, was correlated with a decrease in blood glutamate levels. We therefore suggest that the blood glutamate scavenging activity of GPT and pyruvate contributes to the spectrum of their neuroprotective mechanisms and may serve as a new neuroprotective strategy for the treatment of ischemic stroke.
authors.affiliation: Division of Anesthesiology and Critical Care, Soroka Medical Center, Ben-Gurion University of the Negev, 36 Hanoch Albek Str., Beer-Sheva, Israel 84833. matthewboykoresearch@gmail.com
authors.forename: Matthew
authors.initials: M
authors.lastname: Boyko
authors.forename: Alexander
authors.initials: A
authors.lastname: Zlotnik
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Gruenbaum
authors.forename: Shaun E
authors.initials: SE
authors.lastname: Gruenbaum
authors.forename: Sharon
authors.initials: S
authors.lastname: Ohayon
authors.forename: Ruslan
authors.initials: R
authors.lastname: Kuts
authors.forename: Israel
authors.initials: I
authors.lastname: Melamed
authors.forename: Adi
authors.initials: A
authors.lastname: Regev
authors.forename: Yoram
authors.initials: Y
authors.lastname: Shapira
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Teichberg
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000627:therapeutic use; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000097:blood*; D020244:Infarction, Middle Cerebral Artery / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D062907:Oxaloacetic Acid / Q000627:therapeutic use; D019289:Pyruvic Acid / Q000008:administration & dosage*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D062907:Oxaloacetic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid; D001219:Aspartate Aminotransferases