The Neuroprotective Effects of Oxaloacetate in Closed Head Injury in Rats is Mediated by its Blood Glutamate Scavenging Activity

• DOI: 10.1097/ana.0b013e3181a2bf0b
• Publication Date: 2009-06-15T07:29:02Z
• Authors: Alexander Zlotnik; Shaun E. Gruenbaum; Alan A. Artru; Irene Rozet; Michael Dubilet; Sergey Tkachov; Evgeny Brotfain; Yael Klin; Yoram Shapira; Vivian I. Teichberg
• Keywords: Transaminase

Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of on brain. A number potential mechanisms have suggested explain oxaloacetate-induced neuroprotection. We hypothesize that primary mechanism by which intravenous provides neuroprotection is activation glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby driving force for efflux excess from interstitial fluids into blood. If so, coadministration maleate, a transaminase-blocker expected prevent neuroprotective oxaloacetate.A neurological severity score (NSS) was measured 1 hour closed head (CHI) in rats. Then, rats received 30 microL/min/100 g infusion saline, or mmol/100 solution oxaloacetate, mixture maleate. NSS reassessed at 24 48 CHI. Blood glucose were 0, 60, 90, 120 minutes.NSS improved significantly (P<0.001) only treated oxaloacetate. decreased oxaloacetate-treated group 90 minute (at conclusion administration) (P<0.00001), but not control, maleate oxaloacetate+maleate groups. strong correlation r2=0.86 found exist between percent improvement NSS.The results this study demonstrate activity CHI related its scavenging activity. Management concentration may important implications treatment acute conditions, including stroke.