Medicine and Health Sciences Commons^™

Protein S In Coagulation And Inflammation, Martha Mega Silvia Sim

Theses and Dissertations--Molecular and Cellular Biochemistry

Protein S (PS) is a key regulator, which links inflammation and coagulation and performs multiple proposed functions in both processes. PS exists in the blood as a free soluble form (~40%), bound to complement component 4b-binding protein/ C4BP (~60%), and packaged in platelet α-granules (~2.5%). Subendothelial tissue factor (TF), upon exposure to blood, initiates coagulation, a proteolytic cascade which results in the activation of thrombin, the enzyme responsible for formation of a fibrin clot. PS is a critical anticoagulant that inhibits multiple steps of this process. Only the free fraction of PS has full anticoagulant properties, as C4BP blocks this …

Neuroprotective Strategies Following Experimental Traumatic Brain Injury: Lipid Peroxidation-Derived Aldehyde Scavenging And Inhibition Of Mitochondrial Permeability Transition, Jacqueline Renee Kulbe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) represents a significant health crisis. To date there are no FDA-approved pharmacotherapies available to prevent the neurologic deficits caused by TBI. Following TBI, dysfunctional mitochondria generate reactive oxygen and nitrogen species, initiating lipid peroxidation (LP) and the formation of LP-derived neurotoxic aldehydes, which bind mitochondrial proteins, exacerbating dysfunction and opening of the mitochondrial permeability pore (mPTP), resulting in extrusion of mitochondrial sequestered calcium into the cytosol, and initiating a downstream cascade of calpain activation, spectrin degradation, neurodegeneration and neurologic impairment.

As central mediators of the TBI secondary injury cascade, mitochondria and LP-derived neurotoxic aldehydes make promising …

Pathological Tau As A Cause, And Consequence, Of Cellular Dysfunction, Shelby Meier

Theses and Dissertations--Physiology

Tauopathies are a group of neurodegenerative diseases characterized by the abnormal deposition of the protein tau, a microtubule stabilizing protein. Under normal physiological conditions tau is a highly soluble protein that is not prone to aggregation. In disease states alterations to tau lead to enhanced fibril formation and aggregation, eventually forming neurofibrillary tangles (NFTs). The exact cause for NFT deposition is unknown, but increased post-translational modifications and mutations to the tau gene can increase tangle formation.

Tauopathic brains are stuck in a detrimental cycle, with cellular dysfunction contributing to the development of tau pathology and the development of tau pathology …

Trichloroethylene Exposure And Traumatic Brain Injury Interact And Produce Dual Injury Based Pathology And Pioglitazone Can Attenuate Deficits Following Traumatic Brain Injury, Andrew David Sauerbeck

University of Kentucky Doctoral Dissertations

The development of Parkinson's disease (PD) in humans has been linked to genetic and environmental factors for many years. However, finding common single insults which can produce pathology in humans has proved difficult. Exposure to trichloroethylene (TCE) or traumatic brain injury (TBI) has been shown to be linked to PD and it has also been proposed that multiple insults may be needed for disease development.

The present studies show that exposure to TCE prior to a TBI can result in pathology similar to early PD and that the interaction of both insults is required for impairment in behavioral function, and …

Local Synaptic Network Interactions In The Dentate Gyrus Of A Cortical Contusion Model Of Posttraumatic Epilepsy, Robert F. Hunt Iii

University of Kentucky Doctoral Dissertations

Posttraumatic epilepsy is a common consequence of brain trauma. However, little is known about how long-term changes in local excitatory and inhibitory synaptic networks contribute to epilepsy after closed-head brain injury. This study adapted a widely used model of experimental brain injury as a mouse model of posttraumatic epilepsy. Behavioral seizure activity and alterations in synaptic circuitry in the dentate gyrus were examined in mice after experimental cortical contusion brain injury. Spontaneous behavioral seizures were observed in 20% of mice after moderate injury and 36-40% of mice weeks after severe injury. In the dentate gyrus, most mice displayed regionally localized …

Role Of The Reactive Oxygen Species Peroxynitrite In Traumatic Brain Injury, Ying Deng

University of Kentucky Doctoral Dissertations

Reactive oxygen species (ROS) is cytotoxic to the cell and is known to contribute to secondary cell death following primary traumatic brain injury (TBI). We described in our study that PN is the main mediator for both lipid peroxidation and protein nitration, and occurred almost immediately after injury. As a downstream factor to oxidative damage, the peak of Ca2+-dependent, calpainmediated cytoskeletal proteolysis preceded that of neurodegeneration, suggesting that calpain-mediated proteolysis is the common pathway leading to neuronal cell death. The time course study clearly elucidated the interrelationship of these cellular changes following TBI, provided window of opportunity for pharmacological intervention. …