Anatomy Commons^™

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 …

Air Pollution & The Brain: Subchronic Diesel Exhaust Exposure Causes Neuroinflammation And Elevates Early Markers Of Neurodegenerative Disease, Shannon Levesque, Michael J. Surace, Jacob Mcdonald, Michelle L. Block

Anatomy and Neurobiology Publications

Background

Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood.

Objective

We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology.

Methods

Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months.

Results

DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception …

Chronic Apocynin Treatment Attenuates Beta Amyloid Plaque Size And Microglial Number In Happ(751)Sl Mice, Melinda E. Lull, Shannon Levesque, Michael J. Surace, Michelle L. Block

Anatomy and Neurobiology Publications

Background

NADPH oxidase is implicated in neurotoxic microglial activation and the progressive nature of Alzheimer's Disease (AD). Here, we test the ability of two NADPH oxidase inhibitors, apocynin and dextromethorphan (DM), to reduce learning deficits and neuropathology in transgenic mice overexpressing human amyloid precursor protein with the Swedish and London mutations (hAPP(751)SL).

Methods

Four month old hAPP(751)SL mice were treated daily with saline, 15 mg/kg DM, 7.5 mg/kg DM, or 10 mg/kg apocynin by gavage for four months.

Results

Only hAPP(751)SL mice treated with apocynin showed reduced plaque size and a reduction in the number of cortical microglia, when compared …

Development Of Melanopsin-Based Irradiance Detecting Circuitry, David S. Mcneill, Catherine J. Sheely, Jennifer L. Ecker, Tudor C. Badea, Duncan Morhardt, William Guido, Samer Hattar

Anatomy and Neurobiology Publications

Background

Most retinal ganglion cells (RGCs) convey contrast and motion information to visual brain centers. Approximately 2% of RGCs are intrinsically photosensitive (ipRGCs), express melanopsin and are necessary for light to modulate specific physiological processes in mice. The ipRGCs directly target the suprachiasmatic nucleus (SCN) to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN) to mediate the pupillary light response. How and when this ipRGC circuitry develops is unknown.

Results

Here, we show that some ipRGCs follow a delayed developmental time course relative to other image-forming RGCs. Specifically, ipRGC neurogenesis extends beyond that of other RGCs, and ipRGCs begin …

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 …

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 …

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 …

Membrane-Bound Matrix Metalloproteinases Influence Reactive Synaptogenesis Following Traumatic Brain Injury, Kelly Warren

Theses and Dissertations

Traumatic brain injury (TBI) produces axonal damage and deafferentation, triggering injury-induced synaptogenesis, a process influenced by matrix metalloproteinases (MMP) and their substrates. Here we report results of studies examining the expression and potential role of two membrane-bound MMPs, membrane-type 5-MMP (MT5-MMP) and a disintegrin and metalloproteinase-10 (ADAM-10), along with their common synaptic substrate N-cadherin, during the period of reactive synaptogenesis. Protein and mRNA expression of MT5-MMP, ADAM-10 and N-cadherin were compared in two TBI models, one exhibiting adaptive plasticity (unilateral entorhinal cortex lesion; UEC) and the other maladaptive plasticity (fluid percussion injury + bilateral EC lesions; TBI+BEC), targeting 2, 7, …

Regional Heterogeneity And Diversity Of Astrocytes In Response To Hiv-1 Proteins And Morphine, Wen Chen

Theses and Dissertations

HIV-infected individuals who abuse opiates have been found to have a higher incidence and a faster progression of HIV encephalitis. Astrocytes, the major support cells in the CNS, are known to play a critical role in the HIV neuropathy. Although astrocytes tend not to be productively infected by the HIV-1 virus, dysregulation of their pro- and anti- inflammatory cytokines/chemokines secretion is usually neurotoxic. Glutamate transport in astrocytes is reported to be impaired as well, which result in extrasynaptic excitatory neurotransmitter accumulation and over stimulation of postsynaptic neurons. It is long known that astrocytes from different brain regions have diverse responses …

The Effects Of Bfgf Treatment In The Aged Brain Following Traumatic Brain Injury, Michael Zeigler

Theses and Dissertations

The mature mammalian brain continually generates new neurons in the subventricular zone and hippocampus throughout life. Adult neurogenesis in the hippocampus is associated with hippocampal-dependent learning and memory function. During aging, this endogenous neurogenic potential is reduced which is accompanied by decreased cognitive function seen in the aging population. We have previously found that the injured adult brain shows heightened levels of endogenous neurogenesis and this response is associated with innate cognitive recovery. We have also found that basic fibroblast growth factor (bFGF), a potent neurotrophic polypeptide, can enhance injury-induced hippocampal neurogenesis and improve cognitive recovery following TBI. In this …

Spinal Cord Injury: Exploring The Histology Of Electrospun Implants In Vivo, Charles Lin

Theses and Dissertations

Spinal cord injury results in loss of motor function and sensory perception. A myriad of obstacles prevent axonal regeneration and ultimately functional recovery in those afflicted with spinal cord injury. Combinatorial strategies addressing many of these obstacles simultaneously have shown promising results. Laboratories investigating contusional spinal cord injuries must overcome the formation of a fluid filled cyst, a physical gap that axons must traverse, at the injury epicenter. To fill the cyst, our lab has generated a 3-D electrospun matrix that is capable of directing neurite outgrowth, delivering neurotrophic support, and reducing the activity of neuroinhibitory compounds. These electrospun matrices …

Focal Adhesion Kinase, A Major Regulator Of Oligodendrocyte Morphological Maturation And Myelination, Audrey Lafrenaye

Theses and Dissertations

The formation of the myelin sheath is a crucial step during development because it enables fast and efficient propagation of signals within the limited space of the mammalian central nervous system. During the process of myelination, oligodendrocytes actively interact with the extracellular matrix (ECM). These interactions are considered crucial for proper and timely completion of the myelin sheath. However, the exact regulatory circuits involved in the signaling events that occur between the ECM and oligodendrocytes are currently not fully understood. Therefore, in this dissertation we investigated the role of a known integrator of cell-ECM signaling, namely, focal adhesion kinase (FAK), …

Perifosine, A Novel Akt Inhibitor Induces Apoptosis, Cell Cycle Arrest And Has A Chemo-Sensitizing Effect In Medulloblastoma Cell Lines, Anil Kumar

Theses and Dissertations

Primary central nervous system (CNS) tumors are the most common solid tumors found in children. While surgery and radiotherapy still remain the standard treatment modalities in pediatric brain tumors, chemotherapy also has an important part in the management of these tumors. However, most of the available chemotherapeutic drugs have suboptimal effectiveness. Deregulation of various pro-apoptotic and anti-apoptotic pathways has been cited as a major mechanism underlying this drug resistance. The role of various serine threonine kinases, including Akt kinases, in promoting drug resistance is being extensively studied in various cancers. A complete understanding of the molecular mechanisms that underlie drug …

The Influences Of Matrix Metalloproteinase-1 Expression On Glioblastoma Pathology, Nicholas Pullen

Theses and Dissertations

Glioblastoma multiforme (GBM) is an aggressive central nervous system (CNS) cancer characterized by enhanced tumor cell motility, pernicious invasion into the normal brain, extensive tumor-induced angiogenesis, and adaptive resistance to current therapeutic paradigms. One of the difficulties associated with GBM is the ability of the tumor cells to infiltrate normal CNS tissue. Neurosurgeons can remove the primary tumor mass, but peripheral cells that are inaccessible will ultimately result in a secondary lesion that can lead to death. The matrix metalloproteinases (MMP) are well known for their abilities to facilitate processes of cellular motility and invasion through their clearance of extracellular …

Dendritic Spine Density Varies Between Unisensory And Multisensory Cortical Regions, Moazzum Bajwa

Theses and Dissertations

In the brain, the dendritic spine is a point of information exchange that extends the neuronal surface on which synapses occur, as well as facilitates and stabilizes those contacts. Furthermore, dendritic spines dynamically change in shape and number in response to a variety of factors. Dendritic spine numbers are reduced in mental retardation, enhanced during development, sensory enrichment or physical exercise, or fluctuate during the reproductive cycle. Thus, for a given neuron type, it might be expected that dendritic spine number might achieve a dynamic optimum. Indeed, many studies of spine density of pyramidal neurons in sensory cortex indicate that …

Therapeutic Strategies Aimed To Facilitate Axonal Regeneration And Functional Recovery Following Traumatic Spinal Cord Injury, Woon Chow

Theses and Dissertations

Traumatic spinal cord injury (SCI) is a physically debilitating, emotionally devastating, financially costly, and life-changing condition that afflicts more than 1,000,000 people in the United States alone. Owing to the characteristic neuropathology and low regenerative capacity of the central nervous system, many victims of SCI are left permanently paralyzed. Though the tissue damage caused by the initial insult almost certainly cannot be reversed, intensive research in recent years to elucidate the cellular and molecular events that follows has provided new grounds for optimism. Accordingly, in this dissertation, we present a number of potential treatment strategies aimed to address some of …

Specific Levels Of Therapeutic Ultrasound Stimulate The Release Of Inflammatory And Angiogenic Mediators From Macrophages In Culture, Thomas Turner

Theses and Dissertations

Therapeutic ultrasound (TUS) is a treatment modality that is used to accelerate tissue healing. TUS is thought to affect cellular processes of tissue healing, especially those that occur in the inflammatory and early proliferative phases. TUS can be applied using various parameter selections including intensity, wavelength, duty cycle and treatment duration and no clear consensus exists on optimal parameters for healing enhancement. Macrophages are important mediators of inflammation and their actions are critical to normal progression into the proliferative phase of healing. They complete many functions during these periods of tissue healing, among those being release of cytokines and growth …

Effect Of Posture On Acromiohumeral Distance With Arm Elevation In Subjects With And Without Rotator Cuff Disease Using Ultrasonography, Nitin Kalra

Theses and Dissertations

Objectives: To examine the effects of posture on subacromial (SA) space with arm elevation in patients with rotator cuff disease (RCD) and healthy subjects. Background: Poor posture has been linked to altered scapular mechanics, theorized to lead to excessive SA space narrowing. However, no study has examined the direct effects of posture on SA space using ultrasonography. We hypothesize that when compared to a neutral posture, upright posture will increase SA space and slouched posture will decrease SA space. Methods: Subjects with painful RCD (n=31) and healthy (n=29) shoulders participated. SA space was measured on ultrasound generated images using the …

Structural Interactions Between The Α3Β1 Integrin And Mmp-2: A Potential Functional Role In Cell Adhesion, James Bowman

Theses and Dissertations

During cardiac development and in cardiac disease changes in hemodynamic load initiate events leading to remodeling of the ECM. This study addresses the hypothesis that interactions between Integrins and Metalloprotienases function to modulate cell adhesion in the cultured cardiac fibroblast. The fibroblast is positioned to detect and respond to changes in the mechanical load on the heart. Functionally the cardiac fibroblast is the primary cell type responsible for the production, maintenance, and remodeling of the cardiac interstitium. Matrix Metalloproteinases, specifically the Gelatinases, are expressed in concert during development and in disease with changes in the hemodynamic loading of the heart. …

Investigating The Response Of Oligodendrocyte Progenitor Cells To The Cuprizone Model Of Demyelination, David Moffatt

Theses and Dissertations

Multiple sclerosis and other myelin diseases affect the quality of life many people. In the United States alone, multiple sclerosis afflicts as many as 400,000 individuals. Myelin, which is attacked by multiple sclerosis, plays a critical role in maintaining the healthy function of the adult nervous system. There are many model systems that study myelin and its formation and loss. Our lab investigates the cuprizone model of demyelination and remyelination. The cuprizone model is commonly believed only to affect adult oligodendrocytes, which it kills. The current study investigates whether other cells in the oligodendrocyte line, such as oligodendrocyte progenitor cells, …

Multisensory Input To The Lateral Rostral Suprasylvian Sulcus (Lrss) In Ferret, Elizabeth Hagood

Theses and Dissertations

For the brain to construct a comprehensive percept of the sensory world, information from the different senses must converge onto individual neurons within the central nervous system. As a consequence, how these neurons convert convergent sensory input into multisensory information is an important question facing neuroscience today. Recent physiological studies have demonstrated the presence of a robust population of multisensory neurons in the lateral bank of the rostral suprasylvian sulcus (LRSS) in adult ferret (Keniston et al, 2008). The LRSS is a region situated between somatosensory and auditory cortices, where bimodal (somatosensory-auditory) neurons occupy the greatest percentage of the sensory-responsive …

The Expression And Function Of Phosphacan/Rptpβ In Adaptive Synaptogenesis After Traumatic Brain Injury, Janna Harris

Theses and Dissertations

Traumatic brain injury (TBI) affects 1.5 million Americans annually and is a major health concern. Increasing evidence suggests that the brain extracellular environment regulates plasticity and synaptic recovery following TBI. Here we have focused on phosphacan/RPTPβ, an alternatively spliced group of chondroitin sulfate proteoglycans which are prominent within the mature brain extracellular matrix (ECM). Previous studies show that phosphacan/RPTPβ influences neuronal migration, adhesion, neurite outgrowth, and morphogenesis. However, our understanding of how these important ECM components are involved in recovery from brain trauma remains unclear. In the present study, we used unilateral entorhinal cortex lesion (UEC), a model which induces …

Discovery And Initial Characterizations Of Neurofascin 155 High And Neurofascin 155 Low, Anthony Pomicter

Theses and Dissertations

This thesis contains the findings from four years of research regarding an oligodendrocyte protein named neurofascin 155. The role of this protein in maintaining adhesion between the myelin sheath of oligodendrocytes and the axons of neurons has become well established in recent years and the research presented here has revealed that while western blots have previously shown one protein/band representing neurofascin 155, there are two proteins/bands. These two proteins have been named neurofascin 155 high and neurofascin 155 low due to their previous inclusion in the single band. The work leading up to their discovery, findings, and the relevance of …

Interneuron Subtypes Are Differentially Altered In Malformed, Epileptogenic Cortex, Amanda George

Theses and Dissertations

The propensity for seizures in patients with epilepsy is due to underlying cortical hyperexcitability, the mechanisms of which are poorly understood. Particularly difficult to treat are patients with developmental malformations of cortex. Using the freeze-lesion rat model of one such malformation, polymicrogyria, we identified, in lesioned cortex, alterations in specific interneuron subpopulations that may promote hyperexcitability. Previous studies demonstrate increased excitatory input to the paramicrogyral region. An increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from pyramidal cells has also been shown. We report an increase in sEPSCs recorded from one subtype of interneuron, the low threshold-spiking …

Modeling Pure Vasogenic Edema In The Rat Brain, Charles Nottingham

Theses and Dissertations

Targeted drug delivery to the brain is difficult to achieve using conventional techniques, largely due to the blood-brain barrier’s (BBB) impediment to drug diffusion into the brain parenchyma. In response, development of convection-enhanced delivery (CED) offers the ability to circumvent the BBB and target specific areas of the brain. Predictability of infusate movement in pathological brain states during CED will maximize the effectiveness of this treatment, and therefore modeling of infusate movement must be characterized. Previous work from our lab effectively modeled CED in rats using the middle carotid artery occlusion model of cytotoxic edema. However, previous models examined for …