The effect of photobiomodulation on activity of the human brain

The global aim of this thesis was to explore the effect of photobiomodulation (PBM) on the human brain, with the findings leading hopefully to further establish this treatment as a viable therapeutic option for patients, particularly those with neurodegenerative disease. The results are presented as peer reviewed publications, each with their own chapters (2-5). Chapter 1 contains the literature review, while chapter 6 contains a general discussion. This thesis included functional magnetic resonance imaging (fMRI) research on the effect of PBM on healthy young brains (chapter 2 and 3), along with clinical case studies of patients with neurodegenerative disease (chapter 4) and a thorough systematic review of the effect of PBM on neurodegeneration-induced neuroinflammation (chapter 5). Together, all these components of the thesis offer a robust and diverse exploration of the effect of PBM on healthy and diseased brains. In chapter 2, with the use of fMRI, the effect of PBM on human brain activity in young healthy individuals indicated a reduction in default mode network connectivity during the execution of a task (ie, finger tapping). It was suggested that PBM helped focus attention on the sensorimotor task being undertaken by the individuals. In chapter 3, again with the use of fMRI, the effect of PBM indicated no change in resting state brain connectivity in the brains of healthy individuals. From the results in chapter 2 and 3, it was concluded that in a healthy brain state, PBM had a measurable effect such as altering brain connectivity when the brain is in an evoked task state, for example when undergoing a sensorimotor task, but not during passive rest. In Chapter 4, the effect of PBM on the clinical motor signs and non-motor symptoms of elderly patients with neurodegenerative disease (ie Parkinson’s disease) was observed and recorded. Almost all the signs and symptoms of the patients showed improvement and none got worse. For example, improvement in motor sign

Influence of initial position and stimulus location of the paw on the nociceptive withdrawal reflex in intact rats

Animals have the ability react to noxious stimuli from the environment via a reflex pathway known as the nociceptive withdrawal reflex (NWR). The NWR is a spinal reflex that protects the body from stimuli that may be tissue damaging. In addition, the NWR is known to be supraspinally modulated, which alters the strength of response. Previous studies on the NWR have shown an influence of both stimulus location and initial posture on the NWR. The studies regarding the influence of initial position on the NWR, however, are more limited. Most of the research has been conducted on humans, and in no case has there been studies using intact, unanesthetized rats. The fundamental question this experiment aims to address is whether the initial posture can affect the NWR in intact, unanesthetized rats. Noxious stimuli were provided in the form of heat delivered by a laser for each of the fifteen trials for each rat studied (n=7). The stimuli were aimed at five specific locations on the surface of the rat paw, and the response was recorded with a high speed videocamera positioned under the paw. The response magnitude and direction of the paw movement were quantified by identifying the initial (before NWR) and final (after NWR) position of the raw paw. Similarly, the change in foot angle was also quantified for each of the trials. The results reveal that, unexpectedly, stimulus location did not significantly affect the magnitudes or direction of movement, or the change in foot angle. However, the initial location of the foot did have a significant effect on the withdrawal movement, as stimulation of the foot while it was positioned laterally from the body resulted in medial movement of the foot or stimuli of the foot while it was positioned medially from the body resulted in lateral movement of the foot. In a similar pattern, stimulating the foot while it was positioned rostrally in relation to the body resulted in movement in the caudal direction and stimulating the foot while it was positioned caudally in relation to the body resulted in movement in the rostral direction. The initial angle of the foot was also shown to influence the final angle of the foot, as the angle of the foot changed very little throughout the withdrawal. The results of this study on intact, unanesthetized rats demonstrate that there is evidence that initial position of the rat paw influences the NWR. However, this study was unable to demonstrate that stimulus location influences the NWR. This finding raises the question why stimulus location is not a factor in the rat paw, but has been shown to be a factor in the rat tail and other mammalian studies

Hippocampus

The hippocampus is a bicortical structure with extensive fiber connections with multiple brain regions. It is involved in several functions, such as learning, memory, attention, emotion, and more. This book covers various aspects of the hippocampus including cytoarchitecture, functions, diseases, and treatment. It highlights the most advanced findings in research on the hippocampus. It discusses circuits, pattern formation process of grid cells, and zinc dynamics of the hippocampus. The book also addresses the tau pathology and circRNAs related to Alzheimer’s disease and potential treatment strategies. It is a useful resource for general readers, students, and researchers

Experience-dependent dendrite remodeling of GABAergic interneurons in the adult visual cortex

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 85-97).An ever increasing amount of evidence is demonstrating that structural plasticity is a diverse and ongoing feature that contributes to plasticity in the adult brain. It was previously shown that dendritic arbors of inhibitory interneurons in superficial layer 2/3 can remodel in the adult cortex. Here, we investigated the role of these structural rearrangements during experience-dependent adult plasticity. Using in vivo two photon imaging, we monitored intemeuron dendritic branch tip remodeling in response to changes in visual experience in the adult mouse visual cortex. We find that branch tip dynamics are induced by novel experiences in a stimulus-specific manner. Visual deprivation produces rearrangements that are circuit-specific and are different for branch tips extending into LI or L2/3. The weakening of dendritic input onto these cells functions to reduce levels of inhibition in local cortical circuits. This reduced inhibitory tone provides more salience to remaining instructive input, allowing more structural and functional adaptations to occur. In order to better understand how synaptic plasticity accompanies these dendritic arbor rearrangements as well as other forms of structural plasticity, we developed a method to simultaneously monitor structural and synaptic dynamics in the mammalian brain using in vivo two-photon microscopy. Structural and synaptic components can be labeled in cortical neurons of mice in a cell type and laminar specific manner through co-injection of independent lentiviral vectors at a late embryonic or early postnatal age. We demonstrate that excitatory and inhibitory post-synaptic densities can be visualized by tagging fluorescent proteins to PSD95 and Gephyrin, respectively. Finally, we show that the fluorescent proteins, Teal and Venus, can be simultaneously excited and spectrally resolved through linear unmixing so that individual structural and synaptic components can be identified and followed over time. Through this approach, the relationship between synaptic and structural plasticity can be studied in the living brain.by Jerry L. Chen.Ph.D

The role of nitroxyl in the development of neuropathic pain

Neuropathic pain is a debilitating persistent (chronic) pain condition which affects 2% of the total population, characterised by spontaneous pain (stimulus independent), allodynia (pain generated from non-noxious stimuli) and hyperalgesia (heightened sense of pain to noxious stimuli). Unlike other types of pain such as nociceptive or inflammatory, neuropathic pain is maladaptive and therefore neither protects or supports healing or repair. It is defined as “pain caused by a lesion or disease of the somatosensory nervous system” and can develop following an array of aetiologies such as peripheral or central nerve lesions, diabetes, herpes zoster, HIV and cancer, to name a few. However, resolution of the underlying disease and/or healing of the injury often does not alleviate the associated neuropathic pain symptoms suggesting that central maladaptive plasticity may occur in people with neuropathic pain. Compounding this situation, this maladaptive plasticity often renders traditional analgesics used for nociceptive and inflammatory pain ineffective, thus reducing the treatment options available for neuropathic pain sufferers. The spinal mechanisms which lead to persistent pain development have yet to be fully elucidated. It is well understood that adaptations in the reactivity of spinal glial cells (microglia and astrocytes) may also contribute to central neuronal plasticity, by releasing inflammatory mediators such as nitric oxide and other reactive nitrogen species, that enhance excitatory and/or reduce inhibitory neuronal signalling (also referred to as neuro-immune signalling). Previous limitations in methodology have limited our understanding of longitudinal changes in spinal glial during critical developmental stages in persistent pain pathology. Whether there is a correlation between glial reactivity and neuropathic pain severity during the development of the disease model, has yet to be established. Therefore, the initial aim of this thesis was to determine if reactivity characteristics of spinal microglia may correlate with peripheral injury severity and subsequent neuropathic pain symptoms, in mouse models of persistent pain (Chapter 5). Studies suggest that following peripheral injury, there may be alternative reactive nitrogen species, other than nitric oxide, released by highly reactive glial cells which may facilitate neural plasticity within the spinal cord. The recent development of novel fluorescent tools for measuring reactive nitrogen species, such as nitroxyl, have yet to be used to identify the endogenous presence of this reactive nitrogen species in neuropathic pain development. Therefore, the second aim of this thesis was to validate the use of a novel fluorescent probe for the detection of endogenous nitroxyl in mouse models of persistent pain (Chapter 3). The role of nitroxyl in persistent pain development, has been complicated by recent reports whereby exogenous application of high concentration of this reactive nitrogen species, can act as therapeutic agent for persistent pain. The mechanism of action has yet to be fully elucidated, however nitroxyl is highly reactive towards thiols and metalloproteases which have been implicated in various persistent pain pathways. This led to the subsequent aim of this thesis, which was to determine whether the exogenous nitroxyl donor (Angelis’s salt) may reduce allodynia via its ability to cleave active cysteine residues on lysosomal proteasomes and thus reduce their enzyme function (such as Cathepsin B) in persistent pain mouse models (Chapter 4). The studies offered herein demonstrate that: both the onset time post-injury, and level of microglial reactivity is closely correlated with the severity of peripheral injury and subsequent allodynia; endogenous nitroxyl is produced in models of persistent pain (and other diseases) and can be detected in multiple imaging platforms using novel fluorescent probes; and exogenous nitroxyl donor can reduce both Cathepsin B enzyme activity and allodynia, however Cathepsin B inactivation does not directly account for the reduced allodynia and may not be the pathway involved in this phenomenon. Collectively, these results highlight that there is a correlation between microglial reactivity and the severity of injury and subsequent allodynia which may suggest that physicians should consider the severity of the injury when prescribing treatment and at which timepoint post-injury to best intervene. In addition, novel tools developed at the ARC Centre of Excellence for Nanoscale Biophotonics, University of Adelaide, have provided a way to demonstrate that stimuli used in persistent pain models can generate endogenous nitroxyl which can be semi-quantitatively measured. Furthermore, exogenous nitroxyl donors may reduce allodynia via the in-activation of key thiols and metalloproteases which are critical to persistent pain development. With future research, these novel fluorescent probes may be used in vivo to measure the endogenous nitroxyl output in central glial cells in relation to peripheral injury severity. Furthermore, future work exploring the mechanisms by which exogenous nitroxyl is able to reduce allodynia, could provide a safe therapeutic tool for treating symptoms in neuropathic pain patientsThesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201

Dynamics of non-muscle myosin II organization into contractile networks and fibers at medial cell cortex

The cellular morphology of adhered cells depends crucially on the formation of a contractile meshwork of parallel and cross-linked stress fibers along the contacting surface. The motor activity and mini-filament assembly of non-muscle myosin II is an important component of cell-level cytoskeletal remodeling during mechanosensing. To monitor the dynamics of non-muscle myosin II, we used confocal microscopy to image cultured HeLa cells that stably express myosin regulatory light chain tagged with GFP (MRLC-GFP). MRLC-GFP was monitored in time-lapse movies at steady state and during the response of cells to varying concentrations of blebbistatin (which disrupts actomyosin stress fibers). Using image correlation spectroscopy analysis, we quantified the kinetics of disassembly and reassembly of actomyosin networks and compared to studies by other groups. This analysis suggested the following processes: myosin minifilament assembly and disassembly; aligning and contraction; myosin filament stabilization upon increasing contractile tension. Numerical simulations that include those processes capture some of the main features observed in the experiments. This study provides a framework to help interpret how different cortical myosin remodeling kinetics may contribute to different cell shape and rigidity depending on substrate stiffness. We discuss methods to monitor myosin reorganization using non-linear imaging methods

Optoelectronics – Devices and Applications

Optoelectronics - Devices and Applications is the second part of an edited anthology on the multifaced areas of optoelectronics by a selected group of authors including promising novices to experts in the field. Photonics and optoelectronics are making an impact multiple times as the semiconductor revolution made on the quality of our life. In telecommunication, entertainment devices, computational techniques, clean energy harvesting, medical instrumentation, materials and device characterization and scores of other areas of R&D the science of optics and electronics get coupled by fine technology advances to make incredibly large strides. The technology of light has advanced to a stage where disciplines sans boundaries are finding it indispensable. New design concepts are fast emerging and being tested and applications developed in an unimaginable pace and speed. The wide spectrum of topics related to optoelectronics and photonics presented here is sure to make this collection of essays extremely useful to students and other stake holders in the field such as researchers and device designers

2016 Oklahoma Research Day Full Program

This document contains all abstracts from the 2016 Oklahoma Research Day held at Northeastern State University

Biometric Systems

Because of the accelerating progress in biometrics research and the latest nation-state threats to security, this book's publication is not only timely but also much needed. This volume contains seventeen peer-reviewed chapters reporting the state of the art in biometrics research: security issues, signature verification, fingerprint identification, wrist vascular biometrics, ear detection, face detection and identification (including a new survey of face recognition), person re-identification, electrocardiogram (ECT) recognition, and several multi-modal systems. This book will be a valuable resource for graduate students, engineers, and researchers interested in understanding and investigating this important field of study