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Articles 1 - 30 of 32
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The Effect Of Estrogen And A Mitochondrial Uncoupling Prodrug On Traumatic Brain Injury-Induced Dysfunction In Mice., Olivia J. Kalimon
The Effect Of Estrogen And A Mitochondrial Uncoupling Prodrug On Traumatic Brain Injury-Induced Dysfunction In Mice., Olivia J. Kalimon
Theses and Dissertations--Neuroscience
A large percent of both clinical and pre-clinical traumatic brain injury (TBI) studies report better outcomes females after severe injury compared to males. Mitochondrial dysfunction is a well-characterized driver of secondary injury and an attractive neurotherapeutic target; though, there is limited research available on mitochondrial dysfunction in females. However, a few studies have shown total mitochondria from the cortex of females appear protected from TBI-induced bioenergetic dysfunction. These results were replicated in these studies so further characterization was performed. Additionally, protein expression of some oxidative phosphorylation (OXPHOS) complexes were elevated in the uninjured cortex of females relative to uninjured males, …
Therapeutic Implications Of The Gut-Cns Axis In Promoting Recovery Following Cervical Spinal Cord Injury, Jessica Wilson
Therapeutic Implications Of The Gut-Cns Axis In Promoting Recovery Following Cervical Spinal Cord Injury, Jessica Wilson
Theses and Dissertations--Neuroscience
Nearly 60% of all spinal cord injuries (SCI) occur at the cervical level. These high-level injuries can interrupt the descending respiratory pathways required for breathing. Indeed, therapies in animal studies have been successful at restoring breathing after SCI; however, these interventions appear to be more effective at chronic time points. One potential cause for this observation is the impact of the injury on the gut microbiome. Neurotrauma can induce gut dysbiosis, an imbalance of pathogenic and beneficial gut microbiota, which has previously been shown to negatively impact the central nervous system (CNS) and impair recovery. We aimed to build upon …
Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton
Evaluating The Role Of Mmp9 In Hyperhomocysteinemia Induced Cerebrovascular Pathology, Alexandria Linton
Theses and Dissertations--Neuroscience
Vascular contributions to cognitive impairment and dementia (VCID) is one of the leading causes of dementia, along with Alzheimer’s disease (AD), and often manifests as a comorbidity of AD. Elevated plasma homocysteine, known as hyperhomocysteinemia (HHcy), is a risk factor for VCID; however, the mechanism underlying the connection between HHcy and development of VCID pathology remains elusive. Understanding this mechanism would reveal novel therapeutic targets with the potential to be disease modifying, which are a critical need for a disease that lacks any approved treatment. Previous studies from our lab have strongly associated neuroinflammation and blood brain barrier (BBB) dysregulation …
Evaluating The Microbiome To Boost Recovery From Stroke: The Embrs Study, Tyler Hammond
Evaluating The Microbiome To Boost Recovery From Stroke: The Embrs Study, Tyler Hammond
Theses and Dissertations--Neuroscience
Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and may play a role in stroke rehabilitation. A severely imbalanced microbial community has been shown to occur following stroke, causing a systemic flood of neuro- and immunomodulatory substances due to increased gut permeability and decreased gut motility. Here we measure post-stroke increased gut dysbiosis and how it correlates with gut permeability and subsequent cognitive impairment.
We recruited 12 participants with acute stroke, 12 healthy control participants, and 18 participants who had risk factors for stroke, but had not had a stroke. We measured the gut …
Interleukin-1 Receptor 1 Signaling In Mild Tbi: Do Endothelial Cells Play A Major Role?, Colleen N. Bodnar
Interleukin-1 Receptor 1 Signaling In Mild Tbi: Do Endothelial Cells Play A Major Role?, Colleen N. Bodnar
Theses and Dissertations--Neuroscience
Across the world, over 69 million people sustain a traumatic brain injury (TBI) per year making TBI a major health concern worldwide. Of all the TBIs that occur each year, it is suggested that up to 90 percent are mild in nature. Even a mild TBI causes both physical damages to the cells of the brain and activation of a variety of biochemical cascades. Inflammation is an extremely common pathology seen in the brains of TBI survivors of all severities. Chronic inflammation can cause detrimental effects within the brain including neurodegeneration. A major pro-inflammatory cytokine, interleukin-1 (IL-1), is upregulated within …
Peripheral And Central Glucose Flux In Type I Diabetes, Jelena Anna Juras
Peripheral And Central Glucose Flux In Type I Diabetes, Jelena Anna Juras
Theses and Dissertations--Neuroscience
Diabetes is a complex metabolic disorder, of which high blood glucose concentration is the primary hallmark. Type I diabetes mellitus (T1DM) is characterized by the lack of insulin production, due to a poorly understood autoinflammatory cascade. In the words of historian Barnett “Diabetes may no longer be a death sentence, but for more and more people in the 21st century, it will become a life sentence”, making it the focal point of many research groups. It is estimated that around 20 million individuals worldwide live with T1DM.
Effects of long-term chronically elevated blood glucose are not only seen in micro/macro-vascular …
Examining Human Apoe Genotype And Sex As Modulators Of Respiratory Plasticity In The Presence And Absence Of Spinal Cord Injury, Lydia Ella Strattan
Examining Human Apoe Genotype And Sex As Modulators Of Respiratory Plasticity In The Presence And Absence Of Spinal Cord Injury, Lydia Ella Strattan
Theses and Dissertations--Neuroscience
There are over 17,000 new spinal cord injuries (SCIs) every year in the Unites States alone. Almost 60% of these injuries occur at the cervical level, potentially leading to loss of function in a variety of sensory and motor systems including upper and lower limbs, respiratory, and autonomics. In addition to the physical and emotional costs, individuals who experience these higher level injuries also face a massive financial burden, incurring over $1 million in expenses during the first year after injury in addition to substantial yearly costs for the rest of their lifetime. A myriad of therapeutic approaches targeting plasticity …
Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson
Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson
Theses and Dissertations--Neuroscience
Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Each year, an estimated 2.8 million Americans are diagnosed with a TBI due to falling, motor vehicle collisions, gun violence, and sports related concussions. Although inflicted by a single event, the post-traumatic effects of TBI often develop into a life-long disease. Survivors often experience cognitive decline, memory loss, emotional instability, changes in personality, and physical disabilities. A single TBI, and more-so repetitive TBI's, place an individual at a greater risk of developing chronic neurological disorders, such as dementia or Alzheimer’s disease, earlier in life. …
Integrin Α5Β1 As A Novel Target With The Small Peptide, Atn-161, In The Treatment Of Ischemic Stroke, Danielle Nichele Edwards
Integrin Α5Β1 As A Novel Target With The Small Peptide, Atn-161, In The Treatment Of Ischemic Stroke, Danielle Nichele Edwards
Theses and Dissertations--Neuroscience
Stroke is the 5th leading cause of death and the leading cause of disability in the United States, but there are only two available therapies, tissue plasminogen activator and endovascular thrombectomy. As both therapies focus on removal of the clot, the subsequent pathologic processes, i.e. inflammation, cerebrovascular breakdown, ATP depletion, etc. are left untreated, contributing to worsened patient outcome. Many clinical trials have unsuccessfully attempted to address these mechanisms. The blood-brain barrier (BBB), a system of non-fenestrated endothelial cells, extracellular matrix, and astrocytic endfeet, is significantly impacted after ischemic stroke in its role of preventing the free movement of …
Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford
Autologous Peripheral Nerve Grafts To The Brain For The Treatment Of Parkinson's Disease, Andrew Welleford
Theses and Dissertations--Neuroscience
Parkinson’s disease (PD) is a disorder of the nervous system that causes problems with movement (motor symptoms) as well as other problems such as mood disorders, cognitive changes, sleep disorders, constipation, pain, and other non-motor symptoms. The severity of PD symptoms worsens over time as the disease progresses, and while there are treatments for the motor and some non-motor symptoms there is no known cure for PD. Thus there is a high demand for therapies to slow the progressive neurodegeneration observed in PD. Two clinical trials at the University of Kentucky College of Medicine (NCT02369003, NCT01833364) are currently underway that …
Neuroprotective Strategies Following Experimental Traumatic Brain Injury: Lipid Peroxidation-Derived Aldehyde Scavenging And Inhibition Of Mitochondrial Permeability Transition, Jacqueline Renee Kulbe
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 …
Tgf-Β, Wnt, And Fgf Signaling Pathways During Axolotl Tail Regeneration And Forelimb Bud Development, Qingchao Qiu
Tgf-Β, Wnt, And Fgf Signaling Pathways During Axolotl Tail Regeneration And Forelimb Bud Development, Qingchao Qiu
Theses and Dissertations--Neuroscience
Tgf-β, Wnt, and Fgf signaling pathways are required for many developmental processes. Here, I investigated the requirement of these signaling pathways during tail regeneration and limb development in the Mexican axolotl (Ambystoma mexicanum).
Using small chemical inhibitors during tail regeneration, I found that the Tgf-β signaling pathway was required from 0-24 and 48-72 hours post tail amputation (hpa), the Wnt signaling pathway was required from 0-120 hpa, and the Fgf signaling pathway was required from 0-12hpa. Tgf-β1 was upregulated after amputation and thus may mediate Tgf-β signaling pathway during tail regeneration. Both Smad-mediated and non-Smad mediated Tgf-β signaling …
Studying Vascular Morphologies In The Aged Human Brain Using Large Autopsy Datasets, Eseosa T. Ighodaro
Studying Vascular Morphologies In The Aged Human Brain Using Large Autopsy Datasets, Eseosa T. Ighodaro
Theses and Dissertations--Neuroscience
Cerebrovascular disease is a major cause of dementia in elderly individuals, especially Black/African Americans. Within my dissertation, we focused on two vascular morphologies that affect small vessels: brain arteriolosclerosis (B-ASC) and multi-vascular profiles (MVPs). B-ASC is characterized by degenerative thickening of the wall of brain arterioles. The risk factors, cognitive sequelae, and co-pathologies of B-ASC are not fully understood. To address this, we used multimodal data from the National Alzheimer’s Coordinating Center, Alzheimer’s Disease Neuroimaging Initiative, and brain-banked tissue samples from the University of Kentucky Alzheimer’s Disease Center (UK-ADC) brain repository. We analyzed two age at death groups separately: < 80 years and ≥ 80 years. Hypertension was a risk factor in the < 80 years at death group. In addition, an ABCC9 …
Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron
Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron
Theses and Dissertations--Neuroscience
Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. …
The Default Mode Network And Executive Function: Influence Of Age, White Matter Connectivity, And Alzheimer’S Pathology, Christopher A. Brown
The Default Mode Network And Executive Function: Influence Of Age, White Matter Connectivity, And Alzheimer’S Pathology, Christopher A. Brown
Theses and Dissertations--Neuroscience
The default mode network (DMN) consists of a set of interconnected brain regions supporting autobiographical memory, our concept of the self, and the internal monologue. These processes must be maintained at all times and consume the highest amount of the brain’s energy during its baseline state. However, when faced with an active, externally-directed cognitive task, the DMN shows a small, but significant, decrease in activity. The reduction in DMN activity during the performance of an active, externally-directed task compared to a baseline state is termed task-induced deactivation (TID), which is thought to ‘free-up’ resources required to respond to external demands. …
Novel Targets For Mitochondrial Dysfunction Following Traumatic Brain Injury, Heather M. Yonutas
Novel Targets For Mitochondrial Dysfunction Following Traumatic Brain Injury, Heather M. Yonutas
Theses and Dissertations--Neuroscience
Mitochondrial dysfunction is a phenomenon observed in models of Traumatic Brain Injury (TBI). Loss of mitochondrial bioenergetics can result in diminished cellular homeostasis leading to cellular dysfunction and possible cellular death. Consequently, the resultant tissue damage can manifest as functional deficits and/or disease states. Therapeutic strategies to target this mitochondrial dysfunction have been investigated for models TBI and have shown promising effects.
For this project, we tested the hypothesis that mitoNEET, a novel mitochondrial membrane protein, is a target for pioglitazone mediated neuroprotection. To test this, we used a severe Controlled Cortical Impact (CCI) injury model in mitoNEET null and …
Looking To The Future Of Stroke Treatment: Combining Recanalization And Neuroprotection In Acute Ischemic Stroke, Michael E. Maniskas
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 5th 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 …
Mitochondrial And Neuroprotective Effects Of Phenelzine Related To Scavenging Of Neurotoxic Lipid Peroxidation Products, John Cebak
Theses and Dissertations--Neuroscience
Lipid peroxidation is a key contributor to the pathophysiology of traumatic brain injury (TBI). Traditional antioxidant therapies are intended to scavenge the free radicals responsible for either the initiation or propagation of lipid peroxidation (LP). However, targeting free radicals after TBI is difficult as they rapidly react with other cellular macromolecules, and thus has a limited post-injury time window in which they may be intercepted by a radical scavenging agent. In contrast, our laboratory has begun testing an antioxidant approach that scavenges the final stages of LP i.e. formation of carbonyl-containing breakdown products. By scavenging breakdown products such as the …
Dietary Selenium Supplementation: Effects On Neurodegeneration Following Traumatic Brain And Spinal Cord Injury, Carolyn A. Crowdus Meyer
Dietary Selenium Supplementation: Effects On Neurodegeneration Following Traumatic Brain And Spinal Cord Injury, Carolyn A. Crowdus Meyer
Theses and Dissertations--Neuroscience
Traumatic brain and spinal cord injury continue to be substantial clinical problems with few available treatment strategies. Individuals who are at a greater risk for sustaining a central nervous system (CNS) injury, such as professional athletes and military personnel, may benefit from a prophylactic supplement that would intervene in the neurodegenerative pathways immediately following injury. The high demand for selenium within the central nervous system, as well as the synthesis of selenoproteins by neurons and astrocytes suggests a critical role of selenium within the brain and spinal cord. Studies were designed to test the efficacy of enriched dietary selenium status …
The Intranasal Delivery Of Dnsp-11 And Its Effects In Animal Models Of Parkinson's Disease, Mallory J. Stenslik
The Intranasal Delivery Of Dnsp-11 And Its Effects In Animal Models Of Parkinson's Disease, Mallory J. Stenslik
Theses and Dissertations--Neuroscience
A major challenge in developing disease altering therapeutics for the treatment of Parkinson’s disease (PD) has been the delivery of compounds across the blood-brain barrier (BBB) to the central nervous system (CNS). While direct surgical infusion has been utilized to deliver compounds to the brain that don’t cross the BBB, issues of poor biodistribution in the CNS due in part to properties of the molecules being delivered and/or infusion device protocols have limited the widespread success of this invasive approach. To avoid the issues of surgically delivering compounds to the CNS, numerous studies have examined the use of intranasal administration …
Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown
Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown
Theses and Dissertations--Neuroscience
The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …
Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh
Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh
Theses and Dissertations--Neuroscience
Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca2+ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …
Dopamine And Glutamate Dysfunction In A Rodent Model Of Attention-Deficit/Hyperactivity Disorder: Implications For Future Neuropharmacology, Erin M. Miller
Dopamine And Glutamate Dysfunction In A Rodent Model Of Attention-Deficit/Hyperactivity Disorder: Implications For Future Neuropharmacology, Erin M. Miller
Theses and Dissertations--Neuroscience
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common disorders of childhood. It is theorized to be caused by catecholamine dysfunction in the striatum (Str) and frontal cortex (FC). The spontaneously hypertensive rat (SHR) has been used as a model for ADHD because of its attention deficits, impulsiveness, and hyperactivity. Prior studies of dopamine (DA) in the Str and FC have revealed conflicting results in the SHR compared to control, indicative of a need for a better understanding of DA dynamics in this model. In addition to the DA hypothesis, studies have begun implicating glutamate in the etiology of ADHD. …
Molecular And Cellular Characterization Of Dopamine Neuron Stimulating Peptides, Kristen Kelps
Molecular And Cellular Characterization Of Dopamine Neuron Stimulating Peptides, Kristen Kelps
Theses and Dissertations--Neuroscience
Parkinson’s disease, the second most common neurodegenerative disease, is characterized by the loss of dopaminergic neurons within the substantia nigra. Currently, the treatments available for PD are symptomatic treatments that do not stop the progression of the disease. Trophic molecules, such as glial cell-line derived neurotrophic factor (GDNF), have been evaluated as potential therapeutic molecules that could stop the loss of neurons and potentially restore some of the neurons that have already been lost. However, these trophic molecules are large making them difficult to produce and delivery. Here we characterize three peptides (DNSP-5, DNSP-11, and DNSP-17) to determine it they …
Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne
Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne
Theses and Dissertations--Neuroscience
Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.
Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …
Post-Traumatic Sleep Following Diffuse Traumatic Brain Injury, Rachel K. Rowe
Post-Traumatic Sleep Following Diffuse Traumatic Brain Injury, Rachel K. Rowe
Theses and Dissertations--Neuroscience
Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role …
Dynamic L-Glutamate Signaling In The Prefrontal Cortex And The Effects Of Methylphenidate Treatment, Catherine Elizabeth Mattinson
Dynamic L-Glutamate Signaling In The Prefrontal Cortex And The Effects Of Methylphenidate Treatment, Catherine Elizabeth Mattinson
Theses and Dissertations--Neuroscience
The prefrontal cortex (PFC) is an area of the brain that is critically important for learning, memory, organization, and integration, and PFC dysfunction has been associated with pathologies including Alzheimer’s disease, schizophrenia, and drug addiction. However, there exists a paucity of information regarding neurochemical signaling in the distinct sub-regions of the PFC, particularly the medial prefrontal cortex (mPFC). The mPFC receives glutamatergic input from a number of brain areas, and functional glutamate signaling is essential for normal cognitive processes. To further understand glutamate neurotransmission, in vivo measurements of glutamate were performed in the cingulate cortex, prelimbic cortex, and infralimbic cortex …
Disruptions In The Regulation Of Extracellular Glutamate In The Rat Central Nervous System After Diffuse Brain Injury, Jason Michael Hinzman
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 …
Blast-Induced Brain Injury: Influence Of Shockwave Components, Dexter V. Reneer
Blast-Induced Brain Injury: Influence Of Shockwave Components, Dexter V. Reneer
Theses and Dissertations--Neuroscience
Blast-induced traumatic brain injury (bTBI) has been described as the defining injury of Operations Enduring Freedom and Iraqi Freedom (OEF/OIF). Previously, most blast injury research has focused on the effects of blast on internal, gas filled organs due to their increased susceptibility. However, due to a change in enemy tactics combined with better armor and front-line medical care, bTBI has become one of the most common injuries due to blast. Though there has been a significant amount of research characterizing the brain injury produced by blast, a sound understanding of the contribution of each component of the shockwave to the …
Nigrostriatal Dopamine-Neuron Function From Neurotrophic-Like Peptide Treatment And Neurotrophic Factor Depletion, Ofelia Meagan Littrell
Nigrostriatal Dopamine-Neuron Function From Neurotrophic-Like Peptide Treatment And Neurotrophic Factor Depletion, Ofelia Meagan Littrell
Theses and Dissertations--Neuroscience
Trophic factors have shown great promise in their potential to treat neurological disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has been identified as a potent neurotrophic factor for midbrain dopamine (DA) neurons in the substantia nigra (SN), which lose function in Parkinson’s disease (PD). GDNF progressed to phase II clinical trials, which did not meet proposed endpoints. The large size and binding characteristics of GDNF have been suspected to contribute to some of the shortcomings of GDNF related to delivery to target brain regions. Smaller peptides derived from GDNF (Dopamine-Neuron Stimulating Peptides – DNSPs) have been recently investigated …