Novel Mechanism for Reducing Acute and Chronic Neurodegeneration After Traumatic Brain Injury
Abstract
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 130ug/kg 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2017
- Accession Number
- AD1042683
Entities
People
- Bruce Lyeth
Organizations
- University of California, Davis