Medical Anatomy Commons^™

Looking To The Future Of Stroke Treatment: Combining Recanalization And Neuroprotection In Acute Ischemic Stroke, Michael E. Maniskas

Theses and Dissertations--Neuroscience

Stroke is the 5^th leading cause of death in the U.S. with 130,000 deaths and around 800,000 affected annually. Currently, there is a significant disconnect between basic stroke research and clinical stroke therapeutic needs. Few animal models of stroke target the large vessels that produce cortical deficits seen in the clinical setting. Also, current routes of drug administration, intraperitoneal and intravenous, do not mimic the clinical route of intra-arterial drug administration. To bridge this divide, we have retro-engineered a mouse model of stroke from the current standard of care for emergent large vessel occlusion (ELVO) stroke, endovascular thrombectomy, to …

How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee

University of New Orleans Theses and Dissertations

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the …

Method Of Treating Parkinson's Disease In Humans By Convection-Enhanced Infusion Of Glial Cell-Line Derived Neurotrophic Factor To The Putamen, Stephen S. Gill, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Patents

A method of treating Parkinson's disease in humans is disclosed, wherein glial cell-line derive neurotrophic factor (GDNF) is chronically administered directly to one or both putamen of a human in need of treatment thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter. In one aspect of the present invention the GDNF is infused directly into one or both putamen through one or more indwelling intraparenchymal multiport brain catheters connected to one or more implantable pumps wherein the flow rate is pulsed.

Method Of Treating Parkinson's Disease In Humans By Convection-Enhanced Infusion Of Glial Cell-Line Derived Neurotrophic Factor To The Putamen, Stephen S. Gill, Don M. Gash, Greg A. Gerhardt

Neuroscience Faculty Patents

A method of treating Parkinson's disease in humans is disclosed, wherein glial cell-line derive neurotrophic factor (GDNF) is chronically administered directly to one or both putamen of a human in need of treatment thereof via convection-enhanced infusion using at least one implantable pump and at least one catheter. In one aspect of the present invention the GDNF is infused directly into one or both putamen through one or more indwelling intraparenchymal mutitiport brain catheters connected to one or more implantable pumps wherein the flow rate is pulsed.

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Disruptions In The Regulation Of Extracellular Glutamate In The Rat Central Nervous System After Diffuse Brain Injury, Jason Michael Hinzman

Theses and Dissertations--Neuroscience

Glutamate, the predominant excitatory neurotransmitter in the central nervous system, is involved in almost all aspects of neurological function including cognition, motor function, memory, learning, decision making, and neuronal plasticity. For normal neurological function, glutamate signaling must be properly regulated. Disrupted glutamate regulation plays a pivotal role in the acute pathophysiology of traumatic brain injury (TBI), disrupting neuronal signaling, initiating secondary injury cascades, and producing excitotoxicity. Increases in extracellular glutamate have been correlated with unfavorable outcomes in TBI survivors, emphasizing the importance of glutamate regulation.

The aim of this thesis was to examine disruptions in the regulation of extracellular glutamate …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Characterization And Optimization Of Microelectrode Arrays For Glutamate Measurements In The Rat Hippocampus, Pooja Mahendra Talauliker

University of Kentucky Doctoral Dissertations

An overarching goal of the Gerhardt laboratory is the development of an implantable neural device that allows for long-term glutamate recordings in the hippocampus. Proper L-glutamate regulation is essential for hippocampal function, while glutamate dysregulation is implicated in many neurodegenerative diseases. Direct evidence for subregional glutamate regulation is lacking in previous in vivo studies because of limitations in the spatio-temporal resolution of conventional experimental techniques. We used novel enzyme-coated microelectrode arrays (MEAs) for rapid measurements (2Hz) of extracellular glutamate in urethane-anesthetized rats. Potassium-evoked glutamate release was highest in the cornu ammonis 1 (CA1) subregion and lowest in the cornu ammonis …

Age May Be Hazardous To Outcome Following Traumatic Brain Injury: The Mitochondrial Connection, Lesley Knight Gilmer

University of Kentucky Doctoral Dissertations

Older individuals sustaining traumatic brain injury (TBI) experience a much higher incidence of morbidity and mortality. This age-related exacerbated response to neurological insult has been demonstrated experimentally in aged animals, which can serve as a model to combat this devastating clinical problem. The reasons for this worse initial response are unknown but may be related to age-related changes in mitochondrial respiration.

Evidence is shown that mitochondrial dysfunction occurs early following traumatic brain injury (TBI), persists long after the initial insult, and is severitydependent. Synaptic and extrasynaptic mitochondrial fractions display distinct respiration capacities, stressing the importance to analyze these fractions separately. …

The Underlying Mechanism(S) Of Fasting Induced Neuroprotection After Moderate Traumatic Brain Injury, Laurie Michelle Helene Davis

University of Kentucky Doctoral Dissertations

Traumatic brain injury (TBI) is becoming a national epidemic, as it accounts for 1.5 million cases each year. This disorder affects primarily the young population and elderly. Currently, there is no treatment for TBI, which means that ~2% of the U.S. population is currently living with prolonged neurological damage and dysfunction. Recently, there have been many studies showing that TBI negatively impacts mitochondrial function. It has been proposed that in order to save the cell from destruction mitochondrial function must be preserved. The ketogenic diet, originally designed to mimic fasting physiology, is effective in treating epilepsy. Therefore, we have used …

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. …

The Effect Of Pparγ Activation By Pioglitazone On The Lipopolysaccharide-Induced Pge2 And No Production: Potentialunderlying Alteration Of Signaling Transduction, Bin Xing

University of Kentucky Doctoral Dissertations

Microglia-mediated neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Uncontrolled microglia activation produces major proinflammatory factors including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) that may cause dopaminergic neurodegeneration. Peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone has potent antiinflammatory property. We hypothesize pioglitazone protects dopaminergic neuron from lipopolysaccharide (LPS)-induced neurotoxicity by interacting with relevant signal pathways, inhibiting microglial activation and decreasing inflammatory mediators.

First, the neuroprotection of pioglitazone was explored. Second, the signaling transductions such as jun N-terminal kinase (JNK) and the interference with these pathways by pioglitazone were investigated. Third, the effect of …

Transgenic Mice Which Overexpress Neurotrophin-3 (Nt-3) And Method Of Use, Kathryn M. Albers, Brian M. Davis

Neuroscience Faculty Patents

Transgenic mice express increased levels of neurotrophin-3 (NT-3) in epithelium when their ancestors are microinjected with the NT-3 gene. The NT-3 growth factor expressing transgenic mice are useful in the study of neurodegenerative disorders of the brain such as Parkinson's syndrome and Alzheimer's disease, of the spinal cord motor neurons such as amyotrophic lateral sclerosis, and for testing drug candidates for the treatment of these diseases.

Transgenic Mice Which Overexpress Nerve Growth Factor, Kathryn M. Albers, Brian M. Davis

Neuroscience Faculty Patents

Transgenic mice that express increased levels of nerve growth factor (NGF) in the epidermis and other stratified, keratinized epithelium. The nerve growth factor expressing transgenic mice are useful in the study of neurodegenerative disorders of the brain such as Parkinson's syndrome and Alzheimer's disease and for testing for drug candidates for the treatment of these diseases.

Activation Of Long Descending Propriospinal Neurons In Cat Spinal Cord, Robert J. Adams, Robert D. Skinner, Ronald S. Remmel

Journal of the Arkansas Academy of Science

Isolated mammalian spinal cord has been shown capable of generating locomotor activity. Propriospinal systems assumed to coordinate fore- and hindlimb activity are poorly understood. This study characterizes the long descending propriospinal (LDP) neurons in terms of the location of the somas and their peripheral inputs by direct neuronal recording. Anatomical studies using axonal retrograde transport of horseradish peroxidase from the lumbar to the cervical spinal cord as a tracer first described these neurons. Two hundred and thirty-one LDP neurons were identified in electrophysiological experiments. Of these, 123 responded to natural stimulation, and about 50% of the others were activated only …

Connections Of The Mesencephalic Locomotor Region (Mlr) In The Cat, E. Garcia-Rill, Robert D. Skinner, S. A. Gilmore

Journal of the Arkansas Academy of Science

The cat entopeduncular nucleus (EN), which is the main output of the basal ganglia, is known to project to the mesencephalic tegmentum. We have been able to elicit antidromic responses in single EN neurons from the region of the mesencephalic locomotor region (MLR), then transect (precollicular-postmamillary) the brainstem and elicit rhythmic movements of the limbs by stimulation of the same site in the same animal. Injections of the fluorescent dye 2,4 diamidino phenylindole 2 HCL (DAPI) into this area induces retrograde labeling of cell bodies in EN and motor cortex. Injections of a tritiated amino acid (leucine) into the motor …