title: Blood glutamate scavenging as a novel neuroprotective treatment for paraoxon intoxication.
abstract: Organophosphate-induced brain damage is an irreversible neuronal injury, likely because there is no pharmacological treatment to prevent or block secondary damage processes. The presence of free glutamate (Glu) in the brain has a substantial role in the propagation and maintenance of organophosphate-induced seizures, thus contributing to the secondary brain damage. This report describes for the first time the ability of blood glutamate scavengers (BGS) oxaloacetic acid in combination with glutamate oxaloacetate transaminase to reduce the neuronal damage in an animal model of paraoxon (PO) intoxication. Our method causes a rapid decrease of blood Glu levels and creates a gradient that leads to the efflux of the excess brain Glu into the blood, thus reducing neurotoxicity. We demonstrated that BGS treatment significantly prevented the peripheral benzodiazepine receptor (PBR) density elevation, after PO exposure. Furthermore, we showed that BGS was able to rescue neurons in the piriform cortex of the treated rats. In conclusion, these results suggest that treatment with BGS has a neuroprotective effect in the PO intoxication. This is the first time that this approach is used in PO intoxication and it may be of high clinical significance for the future treatment of the secondary neurologic damage post organophosphates exposure.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Angela
authors.initials: A
authors.lastname: Ruban
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Mohar
authors.affiliation: Department of Biological services, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ghil
authors.initials: G
authors.lastname: Jona
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Teichberg
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000494:pharmacology*; D001930:Brain Injuries / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D062907:Oxaloacetic Acid / Q000494:pharmacology*; D010261:Paraoxon / Q000009:adverse effects* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002800:Cholinesterase Inhibitors; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D062907:Oxaloacetic Acid; D001219:Aspartate Aminotransferases; D010261:Paraoxon