Brain neuroprotection by scavenging blood glutamate

Alexander Zlotnik, Boris Gurevich, Sergei Tkachov, Ilana Maoz, Yoram Shapira, Vivian I. Teichberg

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Excess glutamate in brain fluids characterizes acute brain insults such as traumatic brain injury and stroke. Its removal could prevent the glutamate excitotoxicity that causes long-lasting neurological deficits. As blood glutamate scavenging has been demonstrated to increase the efflux of excess glutamate from brain into blood, we tested the prediction that oxaloacetate-mediated blood glutamate scavenging causes neuroprotection in a pathological situation such as closed head injury (CHI), in which there is a well established deleterious increase of glutamate in brain fluids. We observed highly significant improvements of the neurological status of rats submitted to CHI following an intravenous treatment with 1 mmol oxaloacetate/100 g rat weight which decreases blood glutamate levels by 40%. No detectable therapeutic effect was obtained when rats were treated IV with 1 mmol oxaloacetate together with 1 mmol glutamate/100 g rat. The treatment with 0.005 mmol/100 g rat oxaloacetate was no more effective than saline but when it was combined with the intravenous administration of 0.14 nmol/100 g of recombinant glutamate-oxaloacetate transaminase, recovery was almost complete. Oxaloacetate provided neuroprotection when administered before CHI or at 60 min post CHI but not at 120 min post CHI. Since neurological recovery from CHI was highly correlated with the decrease of blood glutamate levels (r = 0.89, P = 0.001), we conclude that blood glutamate scavenging affords brain neuroprotection Blood glutamate scavenging may open now new therapeutic options.

Original languageEnglish
Pages (from-to)213-220
Number of pages8
JournalExperimental Neurology
Volume203
Issue number1
DOIs
StatePublished - 1 Jan 2007

Keywords

  • Acute brain neurodegeneration
  • Blood glutamate scavenging
  • Brain glutamate levels
  • Closed head injury
  • Glutamate-oxaloacetate transaminase
  • Neurological severity score
  • Neuroprotection
  • Oxaloacetate
  • Spontaneous recovery

Fingerprint

Dive into the research topics of 'Brain neuroprotection by scavenging blood glutamate'. Together they form a unique fingerprint.

Cite this