Nervous System Commons^™

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 …

Pontine Haemorrhage Due To Chondrosarcoma Of The Skull Base, Maliha Iqbal Jumani, Roomasa Channa, Sayed Nabeel Zafar, Ather Enam

Section of Neurosurgery

A young adult presented with acute weakness of right side of body and slurring of speech. An initial brain CT scan showed a pontine haemorrhage, however MRI done a few days later revealed a mass in the left parapharyngeal space. Histopathology of the mass revealed that it was a chondrosarcoma. Subsequently the patient was initially treated with chemotherapy and radiotherapy and later surgery. Skull base chondrosarcomabe is to be included in the differentials of a young patient presenting with signs consistent with pontine haemorrhage.

Interferon Regulatory Factor 3-Dependent Pathways Are Critical For Control Of Herpes Simplex Virus Type 1 Central Nervous System Infection, Vineet D. Menachery, Tracy J. Pasieka, David A. Leib

Dartmouth Scholarship

The initiation of the immune response at the cellular level relies on specific recognition molecules to rapidly signal viral infection via interferon (IFN) regulatory factor 3 (IRF-3)-dependent pathways. The absence of IRF-3 would be expected to render such pathways inoperative and thereby significantly affect viral infection. Unexpectedly, a previous study found no significant change in herpes simplex virus (HSV) pathogenesis in IRF-3^−/− mice following intravenous HSV type 1 (HSV-1) challenge (K. Honda, H. Yanai, H. Negishi, M. Asagiri, M. Sato, T. Mizutani, N. Shimada, Y. Ohba, A. Takaoka, N. Yoshida, and T. Taniguchi, Nature 434:772-777, 2005). In contrast, the …

Central Nervous System Involvement In Multiple Myeloma, Rohana Naqi, Muhammad Azeemuddin, Humera Ahsan

Department of Radiology

Involvement of the central nervous system by multiple myeloma (MM) is considered to be extremely rare. Magnetic Resonauce Imaging (MRI) is the imaging modality of choice to detect and differentiate myeloma at unusual sites. We present the case of a sixty-year-old man who was a known case of MM. In this case report MRI findings of central nervous system in myeloma lesions are reported. The purpose is to increase the awareness of the clinical presentation, neuroradiological findings and follow-up of multiple myeloma with intracranial growth. There are only a few reported cases found concerning MM with intracranial involvement in the …

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, …

Neural Plasticity And Treatment-Induced Recovery Of Sentence Processing In Agrammatism, Cynthia K. Thompson, Dirk B. Den Ouden, Borna Bonakdarpour, Kyla Garibaldi, Todd B. Parrish

Communication Sciences and Disorders Faculty Articles and Research

This study examined patterns of neural activation associated with treatment-induced improvement of complex sentence production (and comprehension) in six individuals with stroke-induced agrammatic aphasia, taking into account possible alterations in blood flow often associated with stroke, including delayed time-to-peak of the hemodynamic response function (HRF) and hypoperfused tissue. Aphasic participants performed an auditory verification fMRI task, processing object cleft, subject cleft, and simple active sentences, prior to and following a course of Treatment of Underlying Forms (TUF; Thompson et al., 2003), a linguistically based approach for treating aphasic sentence deficits, which targeted object relative clause constructions. The patients also were …

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 …

Characterizing Purkinje Cell Responses And Cerebellar Influence On Fluid Licking In The Mouse, Jeri Lonece Bryant

Theses and Dissertations (ETD)

Rodents consume water by performing stereotypical, rhythmic licking movements which are believed to be driven by central pattern generating circuits located in the brainstem. Temporal aspects of rhythmic licking behavior have been shown to be represented in the olivo-cerebellar system in the form of population complex spike activity. These findings suggest that the olivo-cerebellar system is involved in the generating circuitry responsible for licking rhythm in rodents. However, the representation of licking in the simple spike activity of Purkinje cells and the consequences of loss of cerebellar function on licking behavior has not been quantified. I investigated the influence of …

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 …

Progressive Changes In Microglia And Macrophages In Spinal Cord And Peripheral Nerve In The Transgenic Rat Model Of Amyotrophic Lateral Sclerosis, David J. Graber, William F. Hickey, Brent T. Harris

Dartmouth Scholarship

The role of neuroinflammation in motor neuron death of amyotrophic lateral sclerosis (ALS) is unclear. The human mutant superoxide dismutase-1 (hmSOD1)-expressing murine transgenic model of ALS has provided some insight into changes in microglia activity during disease progression. The purpose of this study was to gain further knowledge by characterizing the immunological changes during disease progression in the spinal cord and peripheral nerve using the more recently developed hmSOD1 rat transgenic model of ALS. Using immunohistochemistry, the extent and intensity of tissue CD11b expression in spinal cord, lumbar nerve roots, and sciatic nerve were evaluated in hmSOD1 rats that were …

An Investigation Of The Prevalence Of Upper Limb Neuropathies In Different Types Of College Musicians By Use Of Neurometrix Device, Saunders Jones Jr., Christi Hernandez

Faculty Articles

In general, people who perform repetitive motions are often vulnerable to repetitive strain injuries. Because musicians must execute the same motion over and over again while practicing and performing their music, they are an example of a group that often develops these repetitive strain injuries. More specifically, musicians are known for developing neuropathies in their upper limbs, with carpal tunnel syndrome and cubital tunnel syndrome being most common. However, because of varying playing postures, all musicians may not be at equal risk for developing these two neuropathies, so the purpose of this study was to identify which musician group has …

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 …

Sleep-Disordered Breathing Affects Auditory Processing In 5–7 Year-Old Children: Evidence From Brain Recordings, Alexandra P.F. Key, Dennis L. Molfese, Louise O’Brien, David Gozal

Center for Brain, Biology, and Behavior: Faculty Publications

Poor sleep in children is associated with lower neurocognitive functioning and increased maladaptive behaviors. The current study examined the impact of snoring (the most common manifestation of sleep-disordered breathing) on cognitive and brain functioning in a sample of 35 asymptomatic children ages 5–7 years identified in the community as having habitual snoring (SDB). All participants completed polysomnographic, neurocognitive (NEPSY) and psychophysiological (ERPs to speech sounds) assessments. The results indicated that sub-clinical levels of SDB may not necessarily lead to reduced performance on standardized behavioral measures of attention and memory. However, brain indices of speech perception and discrimination (N1/P2) are sensitive …

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. …

Il-9 As A Mediator Of Th17-Driven Inflammatory Disease, Elizabeth C. Nowak, Casey T. Weaver, Henrietta Turner, Sakhina Begum-Haque, Burkhard Becher, Bettina Schreiner, Anthony J. Coyle, Lloyd H. Kasper, Randolph J. Noelle

Dartmouth Scholarship

We report that like other T cells cultured in the presence of transforming growth factor (TGF) beta, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-beta as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6-producing macrophages in …

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, …

Multiscale Genomic Analysis Of The Corticolimbic System: Uncovering The Molecular And Anatomic Substrates Of Anxiety-Related Behavior, Khyobeni Mozhui

Theses and Dissertations (ETD)

Genetic diversity generates variation at multiple phenotypic levels, ranging from the most basic molecular to higher-order cognitive and behavioral traits. The far-reaching impact that genes have on higher traits is apparent in several neuropsychiatric conditions such as stress and anxiety disorders. Like most, if not all, neural phenotypes, stress, anxiety, and other emotion-related traits are extremely complex and are defined by the interplay of multiple genetic, environmental, experiential, and epigenetic factors.

The work presented in this dissertation is a multi-scalar, integrative analysis of the molecular and neuroanatomic substrates that underlie emotion-related behavior. The amygdala is a principle component of the …

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 …

Frequency And Spatial Characteristics Of Highfrequency Neuromagnetic Signals In Childhood Epilepsy, Jing Xiang, Yang Liu, Yingying Wang, Elijah G. Kirtman, Cincinnati Children’S Hospital Medical Center Kotecha, Yangmei Chen, Xiaolin Huo, Hisako Fujiwara, Nat Hemasilpin, Ki Lee, Francesco T. Mangano, James Leach, Blaise Jones, Ton Degrauw, Douglas Rose

Center for Brain, Biology, and Behavior: Faculty Publications

Purpose. Invasive intracranial recordings have suggested that high-frequency oscillation is involved in epileptogenesis and is highly localized to epileptogenic zones. The aim of the present study is to characterize the frequency and spatial patterns of high-frequency brain signals in childhood epilepsy using a non-invasive technology. Methods. Thirty children with clinically diagnosed epilepsy were studied using a whole head magnetoencephalography (MEG) system. MEG data were digitized at 4 000 Hz. The frequency and spatial characteristics of high-frequency neuromagnetic signals were analyzed using continuous wavelet transform and beamformer. Threedimensional magnetic resonance imaging (MRI) was obtained for each patient to localize magnetic sources. …

Microscopic Analysis Of Sympathetic And Parasympathetic Distribution, Terminal Morphology, And Interaction In Whole-Mount Atria, Scott Harden

Electronic Theses and Dissertations

The sympathetic (SNS) and parasympathetic (PSNS) branches of the autonomic nervous system (ANS) innervate the heart, exerting excitatory and inhibitory influences (respectively) over cardiac functions (heart rate, AV conduction velocity, and contractility). However, the distribution and structure of SNS and PSNS innervation has not yet been well studied. Detailed characterization of the distributional organization and structural morphology of the SNS and PSNS in normal states is essential to the study of pathological autonomic remodeling. The present study utilized double immunohistochemical labeling techniques to examine tyrosine hydroxylase (TH) immunoreactive (IR) SNS and vesicular acetylcholine transporter (VAChT) IR PSNS axons and terminal …