Advisory Committee Chair
Advisory Committee Members
R D Watson
Date of Award
Degree Name by School
Master of Science (MS) College of Arts and Sciences
This project aims to investigate abnormalities in glutamate neurotransmission in the rat cortex following traumatic brain injury (TBI). The overarching hypothesis is that excessive glutamate release originating at the site of injury begins an excitotoxic cascade leading to increased intracellular calcium and cell death. Glutamate, the primary excitatory neurotransmitter in the mammalian central nervous system, facilitates learning, memory, and other cognitive functions via activation of metabotropic and ionotropic glutamate receptors. A family of Na+- dependent excitatory amino acid transporters (EAATs) on the plasma membranes of neurons and glial cells facilitate the rapid removal of glutamate from the synaptic cleft, maintaining basal levels of synaptic glutamate. EAATs are also essential for the maintenance of extracellular glutamate concentrations below toxic levels. High levels of extracellular glutamate can initiate calcium-mediated signaling cascades, likely through activation of extracellular glutamate receptors. Alterations of extracellular glutamate reuptake following TBI may be a critical component in this excitotoxic cascade and presents a possible target for therapeutic intervention. Herein we demonstrated that TBI resulted in decreased EAAT-mediated glutamate reuptake capacity, and possible remolding of astrocytic processes due to injury induced signaling abnormalities. This was evaluated by measuring [3H]-glutamate reuptake and glutamate transporter protein expression profiles. The synaptosomal isolation protocol provides a functional characterization of glutamate clearance following TBI that may allow for the comparison of novel and existing therapeutic drugs.
Dorsett, Christopher, "Abnormalities of Glutamate Neurotransmission Following Traumatic Brain Injury" (2014). All ETDs from UAB. 1544.