Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury
Technical Report,01 Jul 2015,30 Jun 2016
University of Calfornia, Davis Davis United States
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Purpose The purpose of this project is to develop a radically different strategy to reduce brain glutamate excitotoxicity and treat TBI. We will supplement a natural blood-resident enzymatic system with glutamate-oxaloacetate transaminase rGOT and the co-substrate oxalo-acetate OxAc with the objective of reducing blood levels of glutamate. This will produce a brain-to-blood gradient of glutamate which will enhance the removal of excess glutamate from the brain. Scope We will test this novel and powerful neuroprotective treatment in a rat model of repetitive mild concussive TBIs and in a model of a single moderate TBI. Major Findings We have 1.Troubleshooting and refinement of blood serum glutamate assays to reduce variability. 2. Completed statistical analysis of behavioral experiments examining effects of rGOT and rGOT OxAc on outcome on rotarod and Morris watermaze. 3. Measured time course of GOT levels in blood and levels after iv injection of 130ugkg of rGOT. 4.Completed sectioning of brain tissue and completed 60 of hippocampal neuronal cell counting. 5.Troubleshooting and refinement of CSF extraction resulting in reliable measurement of glutamate in CSF.