Medicine and Health Sciences Commons^™

Cardiac Arrest And Global Ischemia Reperfusion Injury: Role Of Mitochondria And Cannabinoid Receptor 2 Signaling., Jennifer L. Bradley

Theses and Dissertations

We explored the effects of cardiac arrest on mitochondria populations and heart whole tissue lysate proteomics utilizing the Weil Institute’s in vivo rat model of cardiac arrest and cardiopulmonary resuscitation. We have discovered that brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Additionally, complex I is the most sensitive electron transport chain complex to ischemic injury and is a major control point of the rate of oxidative phosphorylation following cardiac arrest and cardiopulmonary resuscitation. Preservation of brain mitochondrial activity and function during cardiac arrest may enhance outcomes and recovery.

A recent article focusing on acute myocardial …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain, Olivia J. Choi

Theses and Dissertations

The development of the nervous system is a multi-level, time-sensitive process that relies heavily on cell differentiation. However, the molecular mechanisms that control brain development remain poorly understood. We generated a knockout (KO) mouse for the cilia associated gene Spag17. These animals develop hydrocephalus and enlarged ventricles consistent with the role of Spag17 in the motility of ependymal cilia. However, other phenotypes that cannot be explained by this role were also present. Recently, a mutation in Spag17 has been associated with brain malformations and severe intellectual disability in humans. Therefore, we hypothesized that Spag17 plays a crucial role in …

The Effects Of Long-Term Deafness On Density And Diameter Of Dendritic Spines On Pyramidal Neurons In The Dorsal Zone Of The Feline Auditory Cortex, Rachel J. Bauer

Theses and Dissertations

Neuroplasticity has been researched in many different ways, from the growing neonatal brain to neural responses to trauma and injury. According to recent research, neuroplasticity is also prevalent in the ability of the brain to repurpose areas that are not of use, like in the case of a loss of a sense. Specifically, behavioral studies have shown that deaf humans (Bavalier and Neville, 2002) and cats have increased visual ability, and that different areas of the auditory cortex enhance specific kinds of sight. One such behavioral test demonstrated that the dorsal zone (DZ) of the auditory cortex enhances sensitivity to …

The Role Of A Type Lamins In Regulating Myelination, Jacqueline M. Deloyht

Theses and Dissertations

Multiple sclerosis (MS), a demyelinating disorder of the central nervous system (CNS), affects approximately 400,000 individuals in the United States, and 2.5 million people worldwide. It is a leading cause of disability in young adults. Current treatments for MS target the inflammatory aspects of the disease, but do not aid in remyelination. To address remyelination as a therapeutic strategy, it is imperative to identify mechanisms that regulate myelin formation, including epigenetic targets. In this study, we investigate the role of the LMNA, a gene encoding Lamins A and C, intermediate filaments of the nuclear lamina, in regulating oligodendrocyte development and …

Reverse Engineering A Kinetic Model Of A Dopaminergic Neuron To Apoptosis, Johnathan Morris

Biology and Medicine Through Mathematics Conference

No abstract provided.

An Investigation Of The Efficacy Of Curcumin For Treatment Of Alzheimer's Disease, Parantap Patel

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Curcumin is the primary curcuminoid found in the rhizome of the turmeric plant (Curcuma longa), responsible for the spice’s distinctive yellow color. Research conducted within the past two decades suggests that the compound may be an effective treatment for Alzheimer’s disease, the most prevalent form of dementia affecting nearly 5.2 million Americans. This paper investigates the efficacy of curcumin as treatment for the pathogenesis and symptoms of Alzheimer’s. Research was conducted pertaining to the pathogenesis of Alzheimer’s, the in vitro applications of curcumin, the chemical properties of curcumin, and the in vivo clinical applications of curcumin. The pathogenesis of Alzheimer’s …

Structural Alterations To The Axon Initial Segment Following Diffuse Axonal Injury As A Consequence Of Age, William Behl

Theses and Dissertations

An epidemiological shift towards the elderly population has occurred in traumatic brain injury (TBI). Age is believed to be one of the strongest prognostic indicators following TBI. Diffuse axonal injury (DAI), a prevalent feature of TBI, is believed to be the primary cause for much of the morbidity and mortality associated with TBI. The pathobiology associated with DAI is believed to occur in response to the primary injury in a progressive, secondary fashion. Though the injury mechanisms behind DAI have been shown to occur at numerous sites along the axon, recent work suggests that the axon initial segment (AIS) may …

Exploring Electric Field-Induced Changes In Astrocyte Behavior, Doel Dhar

Theses and Dissertations

Electric fields, which are generated by the movement of charged ions across membranes, are found in all biological systems and can influence cellular components ranging from amino acids to biological macromolecules. Physiological field strengths range from 1 – 200 mV/mm, and these electric fields are especially elevated at sites of cellular growth during development and regeneration. It has previously been demonstrated that elevated electric fields induce alignment of astrocyte processes in vitro, enhancing the rate of neurite outgrowth. It is believed that electric fields of varying physiological strength affect other astrocytic responses associated with regeneration. To characterize the duration over …

Myelin Is Not Required For Maintenance Of The Axon Initial Segment, Anna Josephson

Theses and Dissertations

Axonal pathology is a major contributor to impaired motor, sensory and cognitive dysfunction associated with multiple sclerosis particularly with the progressive forms of the disease. However, the early pathologic events responsible for axonal deterioration remain unclear. It is well recognized that maintaining proper axonal function is intimately related to proper establishment and maintenance of axonal domains such as the node of Ranvier and the axon initial segment (AIS). Numerous laboratories, including ours, have investigated the mechanisms that regulate node of Ranvier formation and maintenance. These studies have shown that node of Ranvier formation and maintenance require myelin contact. Interestingly, many …

Effects Of Short-Term Minocycline Treatments On Inflammatory Cell Response In The Acute Stage Following Tbi, Henna Ayub

Theses and Dissertations

Following traumatic brain injury (TBI), neuroinflammation contributes to the secondary injury. Microglia are the resident immune cells of the central nervous system (CNS), and when activated can exert either protective or detrimental effects on surrounding tissue. They are often segregated into subpopulations based on their type of activation, either pro- inflammatory (M1, classically activated), or anti-inflammatory (M2, alternatively activated). Minocycline, an anti-inflammatory drug, is known to be neuroprotective and to have effect on microglia. However, the effect of minocycline on subpopulations of inflammatory cells in the acute stage following injury is unclear. It is also unclear whether minocycline has a …

Factors That Lead To The Immunotherapy Gap In Multiple Sclerosis Testing, Karthika Solai

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Multiple sclerosis is a disease that affects the central nervous system. Most doctors and scientists believe that it is an autoimmune disease. Simply put, the immune system attacks the nerves in a person’s body, thereby causing myelin damage, inflammation, and neurodegeneration. The plaque that then builds up on the nerves is scar tissue created when the wounds made by the immune system heal. It is this plaque that inhibits communication between the axons in the body and causes the symptoms of MS, which includes problems with movement, pain, vision problems, trouble swallowing, fatigue, and heat sensitivity (Baker et al., 2011, …

Angiogenesis In Response To Varying Fiber Size In An Electrospun Scaffold In Vivo., Damien Brown

Theses and Dissertations

Injury to the spinal cord results in partial or complete loss of sensory perception and motor function. After spinal cord injury (SCI), damaged tissue dies and a cavity will form. This cavity prevents the regeneration of tissue and any functional recovery. One way to address the cavity is the insertion of an electrospun scaffold that our lab has created. This provides a substrate for regenerating tissue to grow on, and it is thought that reestablishing the blood supply within the scaffold will allow cells necessary for regeneration to thrive. This could ultimately lead to meaningful recovery for patients who have …

Combining Electrospun Polydioxanone Scaffolds, Schwann Cells, And Matrigel To Improve Functional Recovery After A Complete Spinal Cord Transection In Rats, Ashok Kannan

Theses and Dissertations

Spinal cord injury (SCI) has presented itself as a multifaceted pathology that is largely inhibitory to regeneration, and therefore to functional recovery, even though spinal cord neurons have been found to be innately regenerative. Thus, having identified the key players in the inhibition of this innate regeneration, SCI researchers have focused on two major types of approaches: (1) blocking inhibitory cues and (2) promoting innate regeneration. Schwann cells (SCs) have long been shown to promote and enhance functional recovery after SCI through providing supplemental myelination and trophic and tropic factors to regenerating axons, though singular approaches rarely address the complex …

Inhibition Of Injury-Induced Cell Proliferation In The Dentate Gyrus Impairs Cognitive Recovery Following Traumatic Brain Injury, Teresa Daniels

Theses and Dissertations

Traumatic brain injury (TBI) induces a robust cellular proliferative response among neural stem/progenitor cells (NS/NPCs) in the dentate gyrus of the hippocampus. This proliferative effect is thought to contribute to the innate cognitive recovery observed following TBI. Inhibition of hippocampal neurogenesis impairs cognitive function. Furthermore, enhancement of injury-induced hippocampal neurogenesis via intraventricular administration of basic fibroblast growth factor (bFGF) improves cognitive function in animals following TBI. In this experiment, we investigated the direct association between injury-induced hippocampal neurogenesis and cognitive recovery utilizing an antimitotic agent, arabinofuranosyl cytidine (Ara-C). In this study, adult rats received a moderate lateral fluid percussion injury …

The Effect Of Minocycline Treatment On Cell Proliferation And Neurogenesis In The Hippocampus In Young And Aged Brains Following Traumatic Brain Injury, Ashley Harvin

Theses and Dissertations

Following traumatic brain injury, there is an enhanced cell proliferative and neurogenic response in the young adult hippocampus, which may be associated with innate cognitive recovery. However, in the aged brain, an increased level of inflammatory cell responses was observed following injury concomitant to decreased hippocampal neurogenesis and cognitive recovery in the aging population. This suggests that excessive inflammation produced in the injured aging brain has a detrimental effect on neurogenesis and cognitive function. In this study, we examined the effect of anti-inflammatory treatment with minocycline on cell proliferation and generation of new neurons in the dentate gyrus (DG) of …

The Role Of Sulfatide In The Development And Maintenance Of The Nodal And Paranodal Domains In The Peripheral Nervous System, Heather Herman

Theses and Dissertations

Sulfatide is a galactolipid and a major lipid component of the myelin sheath. Its production is catalyzed by the enzyme cerebroside sulfotransferase (CST). To determine the functions of sulfatide, the gene encoding CST was genetically disrupted resulting in mice incapable of sulfatide synthesis. Using these mice, it has been shown in the central nervous system (CNS) that sulfatide is essential for normal myelin synthesis and stability even though the onset of myelination is not impaired. Additionally, proper initial clustering of paranodal proteins and cluster maintenance of nodal proteins is impaired suggesting that paranodal domains are important for long-term node stability. …

Early Hearing-Impairment Results In Crossmodal Reorganization Of Ferret Core Auditory Cortex, M. Alex Meredith, Brian L. Allman

Anatomy and Neurobiology Publications

Numerous investigations of cortical crossmodal plasticity, most often in congenital or early-deaf subjects, have indicated that secondary auditory cortical areas reorganize to exhibit visual responsiveness while the core auditory regions are largely spared. However, a recent study of adult-deafened ferrets demonstrated that core auditory cortex was reorganized by the somatosensory modality. Because adult animals have matured beyond their critical period of sensory development and plasticity, it was not known if adult-deafening and early-deafening would generate the same crossmodal results. The present study used young, ototoxically-lesioned ferrets () that, after maturation (avg. = 173 days old), showed significant hearing deficits (avg. …

Group I Metabotropic Glutamate Receptors On Selective Cellular Subtypes In Epileptogenic Malformed Cortex, William Bruch

Theses and Dissertations

Cortical malformations from altered development are common causes of human epilepsy. The cellular mechanisms responsible for the epileptic state of cortex remain unclear and a significant portion of these cases do not respond to treatment. Previous electrophysiological recordings in the Jacobs lab in a rat polymicrogyria model indicated an increased response to group I metabotropic glutamate receptor agonists in the region adjacent to the malformation (PMZ). In addition there was a novel response in low threshold spiking (LTS) interneurons via mGluR5 activation. To determine whether cell specific expression of these receptors was altered in malformed cortex immunohistochemical stains were performed …

Utilization Of Structural And Biochemical Cues To Enhance Peripheral Nerve Regeneration, Balendu Shekhar Jha

Theses and Dissertations

This study examines the prospects of using the electrospinning process to fabricate tissue engineering scaffolds targeting a variety of regenerative applications, with a primary focus on the production of nerve guides for the treatment of long-defect nerve injuries in the peripheral nervous system. A basic overview of the conventional electrospinning process is provided, and the utility of this fabrication scheme in the production of collagen-based tissue engineering scaffolds is demonstrated. Next, a novel modification of the basic electrospinning process is presented. This process, called two pole air gap electrospinning, was developed to produce nerve guides that exhibit an anisotropic structure …

Assessing The Role Of Polyethylene Glycol (Peg) In Improving Functional Recovery Following Spinal Cord Injury, Dustin Dalton

Theses and Dissertations

Injury to the spinal cord results in the disruption of signal transmission between the brain and distal targets. It often presents with the loss of motor function and sensory perception below the level of injury. There are many obstacles following injury that must be overcome in order to encourage axon regeneration and improve functional recovery. A combinatorial approach is necessary to combat physical and chemical barriers to recovery. The fluid filled cyst that forms in the majority of spinal cord injuries presents a physical barrier that we treat with our electrospun bridges. We implanted our bridges into female Long Evans …

Differential Glial Cell Responses In The Dentate Gyrus In Young Adult And Aged Brains Following Traumatic Brain Injury, Christoher Shin

Theses and Dissertations

Traumatic brain injury (TBI) affects 3 out of every 1000 Americans each year, and is the leading cause of morbidity and mortality after trauma, accounting for as many as 56,000 deaths per year (Dutton and McCunn, 2003). The Centers for Disease and Control and Prevention found that TBI most commonly occurs in adolescents and young adults aged from 15 to 24 years and in the elderly (75 years and older). Following injury, the secondary injury begins almost immediately after the primary injury and is the result of a number of cascades where once activated, exacerbate the already altered homeostasis of …

Prenatal Alcohol Exposure Reduces Dendritic Spine Density Across Sensory Cortices, Francis Oppong

Theses and Dissertations

Dendritic spines are the major site of excitatory synapses in cortex, and factors that reduce dendritic spine numbers will produce serious cortical processing deficits, such as has been demonstrated for mental retardation and other psychiatric disorders. Prenatal alcohol exposure also has detrimental effects on brain development that lead to Fetal Alcohol Spectrum Disorder (FASD), which results in reduction of dendritic spine numbers in the hippocampus, prefrontal cortex and somatosensory cortex. FASD also is associated with temporal processing disorders involving sequential auditory stimuli that would be processed in auditory cortical areas. However, it is unknown if the reduction of spine density …

Sulfatide Is Required For Organization Of The Paranode In The Myelinated Axon In The Peripheral Nervous System, Eva Kwong

Theses and Dissertations

Myelin facilitates the timely, efficient conduction of action potentials along axons. Made by Schwann cells (SCs) in the PNS, myelin is unique in that it is composed of a high percentage of lipids, particularly galactolipids. Sulfatide, one such galactolipid, is made by cerebroside sulfotransferase (CST) and has been shown to play a role in organizing paranodal domains in myelinated axons. However less is known regarding the involvement of sulfatide in the establishment and maintenance of the node, of particular interest as it is responsible for the potentiation of action potentials along the axon. Using immunohistochemical and, to a lesser extent, …

The Effects Of Sdf-1Α Treatment On The Migration Of Neural Stem/Progenitor Cells After Traumatic Brain Injury, Corey Evans

Theses and Dissertations

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability among young adults and has been a significant field in medical research over the past decades. Intensive studies focusing on how to repair tissue damage resulting from head injuries have discovered that the central nervous system (CNS) retains a regenerative capacity throughout life due to the persistent presence of neural stem/progenitor cells (NS/NPCs) in the neurogenic regions. In the normal brain, cells generated in the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) to the olfactory bulb and cells in the subgranular zone (SGZ) …

Wilms’ Tumor-1 (Wt1) Protein Expression In Glioma Cells Actuates Cellular Invasiveness- Identifying Its Target Genes, Archana Chidambaram

Theses and Dissertations

Previous studies in our laboratory demonstrated the expression of WT1 in a significant number of glioma cells and established its role in promoting tumor cell proliferation. Here, we noted the effect(s) of manipulating WT1 levels on the expression levels of genes that were previously shown to be regulated by WT1. We found no correlation between the expression levels of WT1 and PDGF-A, Snai1 and E-cadherin and a consistent inverse correlation between WT1 and IGF-1R expression in U251-MG cells. To ascertain whether the increased IGF-1R levels resulting from WT1 silencing could account for decreased cellular proliferation, we utilized siRNA mediated knockdown …

Intrinsic Features Of The Multisensory Cortical Area Lrss In The Ferret, Alexandru Ioan Cojanu

Theses and Dissertations

Environmental events simultaneously transduced by more than one sensory modality underlie multisensory processing in the CNS. While most studies of multisensory processing examine functional effects, none have evaluated the influence of local or columnar circuitry. The goal of the present study is to examine of local features of the ferret lateral rostral suprasylvian sulcus (LRSS), a multisensory cortex. Immunostaining revealed the cytoarchitectonic features of the LRSS: thick supragranular layers, a narrow layer IV, and moderately stained but differentiated infragranular layers. Golgi-Cox techniques were used with light microscopy and digital reconstruction to document neuronal morphology. Among the 90 reconstructed neurons, 4 …

Volumetric Growth Model Of Human Medulloblastoma In The Nude Mouse Cerebellum, Thomas Gavigan

Theses and Dissertations

Medulloblastoma is the most common brain tumor in children, accounting for 10-20% of primary central nervous system (CNS) neoplasms and approximately 40% of all posterior fossa tumors. It is a highly invasive embryonal neuroepithelial tumor that typically arises in the cerebellar vermis and has a tendency to disseminate throughout the CNS early in its course. The molecular mechanisms of the disease largely remain uncharacterized, as the clinical treatment is still associated with mortality and severe side effects. The development of a clinically relevant in vivo model is important not only to further understand the disease but also to provide a …

Novel Roles For Reelin In Retinogeniculate Targeting, Cheryl Haner

Theses and Dissertations

In the developing visual system, the axon of a pre-synaptic cell must be guided to a post-synaptic partner. Retinal ganglion cells (RGCs) in the eye are an excellent model to study this process. Multiple classes exist that respond to specific types of light input, and these project to different destinations in the brain that process distinct types of information. The RGC axons that navigate to the lateral geniculate nucleus (LGN) do so in a class-specific manner. Axons from RGCs that mediate non-image forming functions innervate the ventral LGN (vLGN) and the intergeniculate leaflet (IGL). Axons from RGCs that process image-forming …

Klf2/Klf4 Double Knock-Out Mouse Embryos Show Cranial Bleeding With Endothelial Disruption Of The Primary Head Vein, Benjamin Curtis

Theses and Dissertations

Krüppel-like factors (KLFs) are a family of 3 Cys2/His2 zinc finger transcription factors with a diverse set of roles in cellular differentiation, cell cycle regulation, tumor suppression, erythropoiesis, angiogenesis, and other processes. During embryonic development, KLF2 has a role in vessel maturation. Adult conditional KLF4 knockout mouse embryos have thickened arterial intima follow vascular injury. Breeding KLF2+/- and KLF4+/- mice resulted in the generation of KLF2/KLF4 double knockout (DKO) embryos. KLF2/KLF4 DKO embryos died by E10.5 with cranial bleeding. Using immunohistochemistry, embryo whole-mounts were examined for differences in gross vascularization between wild-type (WT), KLF2-/- and KLF2/KLF4 (DKO embryonic day 9.5 …