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.

Fig. 1

Changes in amplitudes of the EPs after 12.5, 25, 50 mg/kg OxAc administration, respectively. n = 5 animals in experiments with each dosages; data are means ± SEM; *P <0.05, ** P <0.01 for ■ and ▲

Fig. 2

Changes in amplitudes of the EPs after administration of OxAc (12.5 mg/kg), or of GOT (0.14 nmol GOT/100 g rat) and of OxAc (12.5 mg/kg) + GOT (0.14 nmol GOT/100 g rat), respectively. n = 5 animals in experiments with OxAc, GOT and OxAc + GOT, respectively. Data are mean ± SEM; *P <0.05 for ■ and ▲

Fig. 3

Changes of P1 and N1 of EPs 2 h after 50 mg/kg OxAc administration. In control period (before OxAc administration), P1 and N1 were normalized to 100%, n = 5 animals