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Accelerating Peripheral Nerve Regeneration Using Electrical Stimulation Of Selected Power Spectral Densities, Wei-Ming Yu, Madelyn Mccullen, Vincent Chiun-Fan Chen

Engineering Science Faculty Publications

Peripheral nerve injuries are common consequences of extremity trauma or chronic compression with a prevalence of 43.8 per 1 million people (on average) reported in the United States annually, accompanied by a yearly increase in cost of care. Patients suffering from these injuries require surgical procedures and rehabilitative strategies to reinforce their extensive recovery. Several studies have found that the application of electrical stimulation can accelerate peripheral nerve regeneration, thus shortening the time of peripheral nerve growth and reducing the cost of care (Willand et al., 2016). The electrical stimulation paradigms that effectively enhanced functional recovery in most studies employed …

Examining The Effects Of Synthetic Dye Yellow No. 5 (Tartrazine) Exposure On Mouse Neuro2a Neurons In Vitro, Jenna L. Farnum

Honors Undergraduate Theses

Yellow Dye No. 5, also known as tartrazine (TRZ), is widely used[1] and has an accepted daily intake (ADI) of 0-7.5 mg/kg of body weight per day^[2]. Consuming TRZ dosages greater than the ADI can lead to reduced levels of antioxidant enzymes in the brain, chromosomal alterations, or neuronal dendritic changes, [3, 4] which can result in oxidative stress, impaired neuronal functioning and potential mutagenic effects. Within the ADI, there have been observed reductions of the copper zinc superoxide dismutase-1 (SOD1) enzyme levels.[5]We hypothesize that TRZ interacts pre-translationally inside the cell, resulting in the reduction of SOD1 mRNA. …

Invertebrate Retinal Progenitors As Regenerative Models In A Microfluidic System, Caroline D. Pena, Stephanie Zhang, Robert Majeska, Tadmiri Venkatesh, Maribel Vazquez

Publications and Research

Regenerative retinal therapies have introduced progenitor cells to replace dysfunctional or injured neurons and regain visual function. While contemporary cell replacement therapies have delivered retinal progenitor cells (RPCs) within customized biomaterials to promote viability and enable transplantation, outcomes have been severely limited by the misdirected and/or insuffcient migration of transplanted cells. RPCs must achieve appropriate spatial and functional positioning in host retina, collectively, to restore vision, whereas movement of clustered cells differs substantially from the single cell migration studied in classical chemotaxis models. Defining how RPCs interact with each other, neighboring cell types and surrounding extracellular matrixes are critical to …

Emerging Roles Of The Membrane Potential: Action Beyond The Action Potential, Lina Abdul Kadir, Michael Stacey, Richard Barrett-Jolley

Bioelectrics Publications

Whilst the phenomenon of an electrical resting membrane potential (RMP) is a central tenet of biology, it is nearly always discussed as a phenomenon that facilitates the propagation of action potentials in excitable tissue, muscle, and nerve. However, as ion channel research shifts beyond these tissues, it became clear that the RMP is a feature of virtually all cells studied. The RMP is maintained by the cell's compliment of ion channels. Transcriptome sequencing is increasingly revealing that equally rich compliments of ion channels exist in both excitable and non-excitable tissue. In this review, we discuss a range of critical roles …

Engineering Hyaluronic Acid Carbon Nanotube Nanofibers: A Peripheral Nerve Interface To Electrically Stimulate Regeneration, Elisabeth M. Steel

Wayne State University Dissertations

Peripheral nerve injuries annually affect hundreds of thousands of people globally. Current treatments like the gold standard autograft and commercially available nerve guide conduits (NGC) are insufficient to repair long gap peripheral nerve injuries. NGCs can aid recovery but lack key microenvironment cues that promote nerve regeneration. We hypothesized that providing topographical, mechanical, and electrical guidance cues through a nanofibrous composite biopolymer would result in improved neuron growth metrics using an in vitro model. We embedded hydrophilic carbon nanotubes (CNT) within hyaluronic acid (HA) nanofibers by electrospinning. The aims of this study were (1) to define the topographical, nanomechanical, and …

Collective Chemotaxis Of Retinal Neural Cells From Drosophila Melanogaster In Controlled Microenvironments, Stephanie Zhang

Dissertations and Theses

More than 172 million people are influenced by a retinal disorder that stems from either age-related or developmental causes. Of those, 1.5 million people endure a developmental retinal disorder. In the developing retina, neural cells undergo a series of highly complicated differentiation and migration process. A main cause of these diseases is abnormal collective migration of neural progenitors hindering the retinogenesis process. However, our grasp of collective migration and signaling molecules, critical to the developing retina, is incompletely understood. Understanding the molecular mechanisms, such as the fibroblast growth factor pathway, that regulate glial and neuronal migration provides decisive insights in …

Electrical Stimulation With A Conductive Polymer Promotes Neurite Outgrowth And Synaptogenesis In Primary Cortical Neurons In 3d, Qingsheng Zhang, Stephen T. Beirne, Kewei Shu, Dorna Esrafilzadeh, Xu-Feng Huang, Gordon G. Wallace

Australian Institute for Innovative Materials - Papers

Deficits in neurite outgrowth and synaptogenesis have been recognized as an underlying developmental aetiology of psychosis. Electrical stimulation promotes neuronal induction including neurite outgrowth and branching. However, the effect of electrical stimulation using 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. This study examined the effect of 3D electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical stimulation improved neurite outgrowth in 3D neuronal cultures from both wild-Type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95 were elevated under 3D electrical stimulation. Interestingly, 3D electrical stimulation also improved neural cell aggregation as well as …

Analytical Modeling Of A Communication Channel Based On Subthreshold Stimulation Of Neurobiological Networks, Alireza Khodaei

Department of Computer Science and Engineering: Dissertations, Theses, and Student Research

The emergence of wearable and implantable machines manufactured artificially or synthesized biologically opens up a new horizon for patient-centered health services such as medical treatment, health monitoring, and rehabilitation with minimized costs and maximized popularity when provided remotely via the Internet. In particular, a swarm of machines at the scale of a single cell down to the nanoscale can be deployed in the body by the non-invasive or minimally invasive operation (e.g., swallowing and injection respectively) to perform various tasks. However, an individual machine is only able to perform basic tasks so it needs to exchange data with the others …

On Axon-Axon Interaction Via Currents And Fields, Aman Chawla

USF Tampa Graduate Theses and Dissertations

In this dissertation, we investigate coupling between axons in a tract, when the tract has an arbitrary cross-section, with the coupling being mediated by currents as well as electric fields. Under the current mediated setting, we develop a new master equation which captures the relative axonal geometry, specifically, the axon inclinations θ_i and the inter-axon distances W_ip and perform a number of simulations. We observe synchronization in our simulations of axons with differing diameters and separation-dependent coupling delays in the case of non-trivial tract geometries. For the field-mediated interaction setting, we determine the electric near-field of a firing …

Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth Of Primary Prefrontal Cortical Neurons From Nrg1-Ko And Disc1-Li Mice, Qingsheng Zhang, Dorna Esrafilzadeh, Jeremy Micah Crook, Robert M. I Kapsa, Elise M. Stewart, Eva Tomaskovic-Crook, Gordon G. Wallace, Xu-Feng Huang

Australian Institute for Innovative Materials - Papers

Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia. Electrical stimulation using conductive polymers has been shown to stimulate neurite outgrowth of differentiating human neural stem cells. This study investigated the use of the electroactive conductive polymer polypyrrole (Ppy) to counter impaired neurite outgrowth of primary pre-frontal cortical (PFC) neurons from NRG1-knock out (NRG1-KO) and DISC1-locus impairment (DISC1-LI) mice. Whereas NRG1-KO and DISC1-LI exhibited reduced neurite length and number of neurite branches compared to wild-type controls, this was not apparent for cultures on …

Biomaterials Approaches For Utilizing The Regenerative Potential Of The Peripheral Nerve Injury Microenvironment, Melissa Renee Wrobel

Wayne State University Dissertations

Clinically available treatments are insufficient to achieve full functional recovery in large (>3cm) peripheral nerve injuries (PNI). The objectives in this thesis were 1) to study often overlooked elements of intrinsic PNI repair including release of inhibitory CSPGs and post-injury responses of inflammatory macrophages and dedifferentiated Schwann cells; 2) to create biomaterial scaf-folds featuring topographical and adhesive cues to enhance neurite outgrowth; and 3) to test the ability of those cues to direct macrophages and Schwann cells towards a pro-regenerative phe-notype. It is hypothesized that recapitulating the positive and negative cues of the PNI microenvi-ronment can better improve regeneration. …

Identifying And Predicting Rat Behavior Using Neural Networks, Jonathan A. Gettner

Master's Theses

The hippocampus is known to play a critical role in episodic memory function. Understanding the relation between electrophysiological activity in a rat hippocampus and rat behavior may be helpful in studying pathological diseases that corrupt electrical signaling in the hippocampus, such as Parkinson’s and Alzheimer’s. Additionally, having a method to interpret rat behaviors from neural activity may help in understanding the dynamics of rat neural activity that are associated with certain identified behaviors.

In this thesis, neural networks are used as a black-box model to map electrophysiological data, representative of an ensemble of neurons in the hippocampus, to a T-maze, …

Evaluation Of Mems Fabricated Fractal Based Free Standing Scaffolds For The Purposes Of Developing A Brain Bioreactor, Brandy Broadbent

Wayne State University Theses

The brain is the most complex organ in the body due to the multiple cell types,

billions of tightly packed synapses, extracellular matrix, and intricate topography. Microelectrical-mechanical

fabrication techniques exhibit promise in the field of neuronal

tissue engineering because the shape is highly controllable and a variety of materials can

be used in creation of bioreactors. This work evaluates the ability of a free standing TiO2

coated fractal scaffold to support healthy neuronal growth. Also evaluated is the

propensity for the neurons to take advantage of the 3D growing surface without the use of

complex extracellular matrix factors over the …

In Vivo Mri Signatures Of Hippocampal Subfield Pathology In Intractable Epilepsy., Maged Goubran, Boris C Bernhardt, Diego Cantor-Rivera, Jonathan C Lau, Charlotte Blinston, Robert R Hammond, Sandrine De Ribaupierre, Jorge G Burneo, Seyed M Mirsattari, David A Steven, Andrew G Parrent, Andrea Bernasconi, Neda Bernasconi, Terry M Peters, Ali R Khan

Robarts Imaging Publications

OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo.

EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively …

Pre-Differentiation Of Human Neural Stem Cells Into Gabaergic Neurons Prior To Transplant Results In Greater Repopulation Of The Damaged Brain And Accelerates Functional Recovery After Transient Ischemic Stroke, Hima C. S Abeysinghe, Laita Bokhari, Anita F. Quigley, Mahesh A. Choolani, Jerry Chan, Gregory J. Dusting, Jeremy M. Crook, Nao R. Kobayashi, Carli Roulston

Australian Institute for Innovative Materials - Papers

2015 Abeysinghe et al. Introduction: Despite attempts to prevent brain injury during the hyperacute phase of stroke, most sufferers end up with significant neuronal loss and functional deficits. The use of cell-based therapies to recover the injured brain offers new hope. In the current study, we employed human neural stem cells (hNSCs) isolated from subventricular zone (SVZ), and directed their differentiation into GABAergic neurons followed by transplantation to ischemic brain. Methods: Pre-differentiated GABAergic neurons, undifferentiated SVZ-hNSCs or media alone were stereotaxically transplanted into the rat brain (n=7/group) 7 days after endothelin-1 induced stroke. Neurological outcome was assessed by neurological deficit …

Nanosecond Pulsed Electric Field Thresholds For Nanopore Formation In Neural Cells., Caleb C Roth, Gleb P Tolstykh, Jason A Payne, Marjorie A Kuipers, Gary L. Thompson Iii, Mauris N Desilva, Bennett L Ibey

Henry M. Rowan College of Engineering Faculty Scholarship

The persistent influx of ions through nanopores created upon cellular exposure to nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal function. One ion, calcium (Ca(2+)), is important to action potential firing and regulates many ion channels. However, uncontrolled hyper-excitability of neurons leads to Ca(2+) overload and neurodegeneration. Thus, to prevent unintended consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure parameters is required. We determined the relationship between nsPEF exposure parameters (pulse width and amplitude) and nanopore formation in two cell types: rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We identified thresholds for nanoporation using …

Engineering Microenvironments To Modulate Calcium Information Processing In Neuronal Cells, Kinsey Cotton Kelly

Doctoral Dissertations

Tissue engineered microenvironments were constructed to test the effects glial cells have on calcium information processing, and to mimic conditions in vivo for tumor invasion and residual cancer after resection of tumor. Submaximal, nM, glutamate (GLU) stimuli were applied to the engineered environments, and the resulting calcium dynamic behavior of neuronal cells was measured to help predict and interpret chaotic systems in the experimental realm. Calcium is a key signaling ion which signals through the N-methyl-D-aspartate (NMDA) glutamate receptor on the neuronal membrane. GLU binding to the NMDA receptor (NMDAR) causes a large and dynamic increase in neuronal intracellular calcium. …

A Depolymerization Based Model Of Neuron Growth Cone Shape And Motility, Neerajha Nagarajan

Master's Theses

Cell migration is a ubiquitous process underlying critical biological mechanisms like wound healing, cancer metastasis and even neuron growth cone motility. It is a critical process for the living organisms as it ensures proper functioning of the system, for example, crawling fibroblasts endure closure of wounds during wound healing. Here we focus our interest on neuron growth cones, a sensory and motile organelle present at the tip of extending neurites, like the axons, in neurons. These are responsible for neuron pathfinding onto specific targets and synapses, in responses to various guidance cues. Interestingly, the motility of the growth cones is …

Adaptive Local And Global Synchronization And Phase Control Of Inferior Olive Neurons (Ions), Srujan Kumar Chalike

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clusters of inferior olive neurons (IONs) in the olive-cerebellar system play an important role in providing synchronized motor control signals for the activation of large number of muscles. However, the dynamics of IONs are highly nonlinear and the system parameters are assumed to be unknowm. The IONs evolving from arbitrary initial conditions are not synchronized. However the application of IONs for control of BAUV's requires that IONs oscillate in unison. The objective is to design control laws such that the controlled ION tracks the trajectories of the reference ION. The two control laws are derived based on tuning functions adaptive …

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Rajanikanth Vadigepalli

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …

Surface-Modified Plga Nanoparticles For Targeted Drug Delivery To Neurons, Jingyan Li

LSU Master's Theses

The blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease such as Parkinson’s Disease (PD). Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable poly (lactic-co-glycolic acid) (PLGA) and poly (lactic acid) (PLA) nanoparticles for drug delivery across the BBB. Recent advances on PLGA/PLA NPs enhanced neural delivery of …

Artificial Neural Network Modeling Of Ddgs Flowability With Varying Process And Storage Parameters, Rumela Bhadra, K. Muthukumarappan, Kurt A. Rosentrater

Kurt A. Rosentrater

Neural Network (NN) modeling techniques were used to predict flowability behavior in distillers dried grains with solubles (DDGS) prepared with varying CDS (10, 15, and 20%, wb), drying temperature (100, 200, and 300°C), cooling temperature (-12, 0, and 35°C) and cooling time (0 and 1 month) levels. Response variables were selected based on our previous research results, and included aerated bulk density, Hausner Ratio, Angle of Repose, Total Flowability Index, and Jenike Flow Function. Various neural network models were developed using multiple input variables in order to predict single response variables or multiple response variables simultaneously. The NN models were …

Robust Dynamic Balance Of Ap-1 Transcription Factors In A Neuronal Gene Regulatory Network., Gregory M Miller, Babatunde A Ogunnaike, James S Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: The octapeptide Angiotensin II is a key hormone that acts via its receptor AT1R in the brainstem to modulate the blood pressure control circuits and thus plays a central role in the cardiac and respiratory homeostasis. This modulation occurs via activation of a complex network of signaling proteins and transcription factors, leading to changes in levels of key genes and proteins. AT1R initiated activity in the nucleus tractus solitarius (NTS), which regulates blood pressure, has been the subject of extensive molecular analysis. But the adaptive network interactions in the NTS response to AT1R, plausibly related to the development of …