Abstract
This study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent.
Highlights
Exposure to organophosphate nerve agents causes a set of severe symptoms, such as seizures that rapidly progress to status-epilepticus, which leads to profound structural brain damage [1]
The field of view of the the image was 4 × 4 cm2; (D) Axial MR image of the rat brain obtained by rapid acquisition with relaxation enhancement (RARE) sequence showing the position of the selected voxel (4 × 4 × 4 mm3) covering predominantly the hippocampus region
The current study confirmed the mechanism of blood glutamate scavenging (BGS) as an agent that accelerates the natural process of brain to blood glutamate efflux, following PO intoxication
Summary
Exposure to organophosphate nerve agents causes a set of severe symptoms, such as seizures that rapidly progress to status-epilepticus, which leads to profound structural brain damage [1]. Much of the brain damage does not typically occur at the time of the initial lesion, making secondary neurological damage a major contributor to the neuronal loss [2]. This damage is partially related to the release of excessive amounts of glutamate (Glu) into the brain interstitial/cerebrospinal fluid (ISF/CSF) [3]. The present study is based on our previous findings that excess brain glutamate can be reduced by the application of a novel blood glutamate scavenging (BGS) treatment that rapidly decreases glutamate levels in the blood, thereby increasing the driving force for Glu fluxes from brain ISF/CSF to the blood [9]. The rapid decrease of plasma Glu levels is achieved by the intravenous administration of a recombinant preparation of glutamate oxaloacetate transaminase (rGOT) in combination with low amounts of the co-substrate oxaloacetate (OxAc)
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