Effects of Blood Glutamate Scavenging on Cortical Evoked Potentials

Abstract

It is well known that traumatic or ischemic brain injury is followed by acute excitotoxicity caused by the presence of abnormally high glutamate (Glu) in brain fluids. It has recently been demonstrated that excess Glu can be eliminated from brain into blood following the intravenous administration of oxaloacetate (OxAc), which, by scavenging blood Glu, induces an enhanced and neuroprotective brain-to-blood Glu efflux. In this study, we subjected rats to intravenous OxAc administration (i.v., 12.5, 25, and 50 mg/kg, respectively), and studied its effects on somatosensory evoked cortical potentials (EPs). Against our expectation, the amplitudes of EPs did not decrease but increased in a dose- and time-dependent manner after OxAc administration. Similar effects were observed when blood Glu scavenging was enhanced by combining OxAc (12.5 mg/kgbw) with recombinant glutamate-oxaloacetate transaminase (GOT, 0.14 nmol/100 g rat). On the basis of these results, we suggest that the changes of amplitudes of the EPs involve not only a glutamatergic but also the weakening of a GABAergic component. We cannot rule out the possibility that OxAc penetrates into the brain and improves mitochondrial functions.

The effects of hemodialysis on blood glutamate levels in chronic renal failure: Implementation for neuroprotection

“…Previous studies done by our group and others have shown that pharmacologically reducing blood glutamate levels with glutamate scavengers (such as oxaloacetate and pyruvate) limit glutamate neurotoxicity and provide better neurologic outcomes after various brain insults, particularly traumatic brain injury [14,[19][20][21][44][45][46][47][48][49][50][51][52][53]. Unfortunately, although these treatments have been shown to be effective in animal models of stroke, traumatic brain injury, and subarachnoid hemorrhage, their use in humans is limited by Food and Drug administration restrictions.…”

Glutamate as a neurotransmitter in the healthy brain

“…On the other hand, there is an efflux mechanism for glutamate as blood-mediated scavenging is reported to reduce glutamate in the cerebrospinal fluid (Gottlieb et al 2003). There is some evidence that this may offer some protection (Zlotnik et al 2008; Teichberg et al 2009; Zlotnik et al 2010; Nagy et al 2010). The mechanism, however, of release from the brain remains to be identified.…”

Is there a role for glutamate-mediated excitotoxicity in inflammation-induced depression?

“…60 Blood glutamate scavenging can be enhanced further by adding recombinant GOT to oxaloacetate. 61,62 The ability of blood glutamate scavenging to decrease brain glutamate levels was demonstrated in vivo in a model of brain ischemia in the rat using magnetic resonance spectroscopy. 63 The neuroprotective effect of blood glutamate scavenging has been confirmed in a number of experimental conditions associated with high brain concentrations of glutamate, such as traumatic brain injury, epilepsy, and ischemic stroke.…”