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, 2016
- Accession Number
- AD1016853
Entities
People
- Bruce Lyeth