abstract: Spinal cord injury (SCI) disrupts the communication between supraspinal circuits and spinal circuits distal to the injury. This disruption causes changes in the motor abilities of the affected individual, but it can also be used as an opportunity to study motor control in the absence or limited presence of control from the brain. In the case of incomplete paraplegia, locomotion is impaired and often results in increased incidence of foot drag and decreased postural stability after injury. The overall goal of this work is to understand how changes in kinematics of movement and neural control of muscles effect locomotor coordination following SCI. Toward this end, we examined musculoskeletal parameters and kinematics of gait in rats with and without incomplete SCI (iSCI) and used an empirically developed computational model to test related hypotheses. The first study tested the hypothesis that iSCI causes a decrease in locomotor and joint angle movement complexity. A rat model was used to measure musculoskeletal properties and gait kinematics following mild iSCI. The data indicated joint-specific changes in kinematics in the absence of measurable muscle atrophy, particularly at the ankle as a result of the injury. Kinematic changes manifested as a decrease in complexity of ankle motion as indicated by measures of permutation entropy. In the second study, a new 2-dimensional computational model of the rat ankle combining forward and inverse dynamics was developed using the previously collected data. This model was used to test the hypothesis that altered coordination of flexor and extensor muscles (specifically alteration in burst shape and timing) acting at the ankle joint could be responsible for increases in incidence of foot drag following injury. Simulation results suggest a time course for changes in neural control following injury that begins with foot drag and decreased delay between antagonistic muscle activations. Following this, beneficial adaptations in muscle activation profile and ankle kinematics counteract the decreased delay to allow foot swing. In both studies, small changes in neural control caused large changes in behavior, particularly at the ankle. Future work will further examine the role of neural control of hindlimb in rat locomotion following iSCI. / Dissertation/Thesis / Ph.D. Bioengineering 2012

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A lesÃo medular ocasiona diversas dificuldades ou necessidades de ajuda na realizaÃÃo das mais diferentes atividades da vida diÃria nas pessoas acometidas. Ao proporcionar um cuidado de enfermagem para ajudar a pessoa portadora de lesÃo medular, se obtÃm um exemplo de reflexÃo acerca da qualificaÃÃo da prÃtica profissional, promoÃÃo da saÃde e melhoria do bem-estar destas pessoas. Contrariando a tendÃncia de nÃo valorizar o uso de teorias de enfermagem, objetivou-se analisar a aplicabilidade da Teoria de Enfermagem ClÃnica de Ernestine Wiedenbach na identificaÃÃo da necessidade de ajuda Ãs pessoas com paraplegia. Trata-se de um estudo exploratÃrio, descritivo e de natureza qualitativa que permite uma compreensÃo da experiÃncia humana subjetiva da vida destes seres. Os sujeitos pesquisados perfizeram um total de nove pessoas com paraplegia atravÃs de triagem realizada seguindo critÃrios de inclusÃo. O lÃcus foi o domicÃlio, uma vez que à um ambiente que promove maior privacidade e confiabilidade para a coleta de informaÃÃes. Os instrumentos escolhidos foram um formulÃrio estruturado constando dados socioeconÃmicos, de identificaÃÃo do sujeito da pesquisa e especÃficos sobre a lesÃo medular e uma entrevista semi-estruturada que abordou questÃes sobre o significado de ajuda, quais necessidades de ajuda enfrentam estes sujeitos, qual ajuda necessÃria pretendem receber, de quem estÃo recebendo ajuda e se algum enfermeiro o havia ajudado. A entrevista foi gravada respeitando-se todos os critÃrios Ãticos de pesquisa com seres humanos e os dados foram posteriormente transcritos e agrupados em categorias seguindo a abordagem metodolÃgica de Bardin da anÃlise de conteÃdo dos relatos. Assim, foram criadas quatro categorias: 1- A percepÃÃo do que à ajuda pelos portadores de paraplegia e o cuidado de enfermagem; 2- A identificaÃÃo das necessidades de ajuda; 3- Ofertando a ajuda: os significados e 4- A ajuda esperada pelos portadores de paraplegia. Os dados demonstraram que os portadores de paraplegia entendem a ajuda como, cooperaÃÃo, incentivo, motivaÃÃo, apoio ou atà mesmo uma forma de preconceito ou exclusÃo. Quanto Ãs necessidades de ajuda, as identificadas foram: Acessibilidade; Preconceito que percebem das pessoas; Sentimento de impotÃncia diante das dificuldades; Higiene Pessoal e Ãntima; Privacidade na execuÃÃo de cuidados de higiene Ãntima; InfecÃÃo urinÃria; Cateterismo vesical; Medo; Dor neuropÃtica; Espasticidade; Problemas financeiros; Falta de emprego; Uso de medicaÃÃes orais; e Falta de adaptaÃÃo no domicÃlio. Quanto à ajuda que recebem foram apontados a dos amigos e da famÃlia. Ao serem perguntados se algum enfermeiro ofertou alguma ajuda no percurso de sua condiÃÃo de paraplegia obteve-se como resposta os profissionais do centro de reabilitaÃÃo. AlÃm disso, foi proposto um plano de cuidados para a prÃxis de enfermeiros no cuidado domiciliar a pessoas com paraplegia. Considera-se que este estudo trouxe uma grande contribuiÃÃo cientÃfica visto que comprovou a eficÃcia da Teoria de Wiedenbach para a implementaÃÃo de cuidados de enfermagem direcionados a pessoas com lesÃo medular e ainda elaborou um modelo de processo de enfermagem voltado para portadores de paraplegia, podendo ser executado no prÃprio domicÃlio, corroborando com a proposta de promoÃÃo da saÃde, reintegraÃÃo e suporte sÃcio-espiritual do cuidar humanizado preconizado pela ciÃncia da Enfermagem.

It was hypothesized that superparamagnetic nanoparticles encapsulated in a silica shell with a fluorescent dye could be functionalized with axonal tracers and could be used for serial, non-invasive imaging with magnetic resonance imaging (MRI) for axon tract tracing. Nanoparticles functionalized with amine, octadecyl, silica, and biotinylated dextran amine were manufactured and characterized with MRI, scanning electron microscopy, and UV-visible, infrared, and fluorescence spectroscopy. Nanoparticle concentrations of 10 mM were not toxic to adult rat neural progenitor cells (NPCs) and labeled approximately 90% of cells. Nanoparticles were assessed for anterograde and retrograde tract tracing in adult rat models. With MRI and microscopy, the nanoparticles did not appear to trace axons but did provide an MRI signal for up to 3 weeks post implantation. While functionalized nanoparticles did not appear to trace axons, they are not toxic to NPCs and may be used as a MRI contrast agent in the neural axis.

Foi realizado estudo experimental com ratos Wistar Albinos, com o objetivo de avaliar diferentes modelos de estudo da lesão da medula espinhal. Os controles foram formados pelos grupos Anestesia, Divulsionamento dos tecidos moles pré-vertebrais e Laminectomia. Os grupos para estudo da lesão da medula espinhal foram formados por animais nos quais o segmento vertebral localizado entre T10 e L1 foi submetido à secção total da medula espinhal, secção parcial (hemissecção), secção total precedida da aplicação local de anestésico e compressão vertebral. Os animais foram avaliados 2 e 24 horas após a realização dos procedimentos, por meio da Escala de Avaliação Locomotora, Teste do Campo Aberto, Teste de Retirada da Cauda, Teste da Placa Quente e Teste do Pinçamento da Pata (reflexos segmentares e supra-segmentares) e também por métodos histológicos, utilizando-se as colorações de Níssl, HematoxHina-Eosina e Glees. Foi observado que as escalas de avaliação locomotora utilizadas foram menos sensíveis à detecção de mudanças funcionais nos animais se comparadas com os testes de comportamento sensório-motores. O teste Exploração no Plano Vertical foi o mais sensível para detectar deficiências sensório-motoras nos diferentes grupos experimentais. Por esse método detectamos uma diminuição da capacidade de exploração do plano vertical nos animais 24 horas após os procedimentos. O teste de função reflexa mais sensível à detecção de deficiências sensório-motoras nos animais após trauma raquimedular leve, moderado e grave, foi o Teste da Placa Quente. Portanto, este estudo demonstrou que, além das Escalas de Avaliação Locomotora, o Teste do Campo Aberto e o Teste da Placa Quente são de utilização fácil, simples, barata, reprodutível e quantitativa, com sensibilidade para detectar deficiências funcionais em animais que tenham sofrido trauma raquimedular leve, moderado ou grave. A análise histológica em segmentos da medula espinhal abrangendo o sítio da lesão permitiu a avaliação da lesão e correlação entre a lesão sensitiva e motora. / An experimental study was carried out using Wistar Albine rats, aiming at an evaluation of different models for the study of spinal injury. Controls included the following groups: Anesthesia, Divulsion of the soft prevertebral tissues and Laminectomy. Groups for the study of spinal injury were composed by animals whose vertebral segment between T10 and L1 was submitted to Total Section of the Spinal cord, Partial Section (hemissection), Total Section Preceded of Application of Local Anesthetic and Vertebral Compression. Animals were evaluated, 2 and 24 hours after the experimental procedures, by means of the Locomotor Evaluation Scale, Open Field Test, Tail Flick Test, Hot Plate Test and Paw Nippering Test (segmentary and suprasegmentary reflex), as well as by means of histological methods using Níssl, Hematoxilin-Eosin and Glees Stainning. lt was observed that the Locomotor Evaluation Scales so far used were less sensitive to detection of functional changes in animals when compared with the sensorio-motor behaviour tests. The vertical Plain Exploration Test was the most sensitive for detection of sensorio-motor deficiences in different experimental groups. By means of this method we could detect a decrease in the ability to explore the Vertical Plain in the animals of 24 hours. The more sensitive reflex function test to detect sensorio-motor deficiences of animals, following light, moderate or severe spinal cord injury, was the Hot Plate Test. Therefore, this study showed that, in addition to the locomotor Evaluation scales, the Open Field Test and Hot Plate Test are of easy, simple, cheap, reproducible and quantitative utilization, showing enough sensitivity to detect functional deficiences in animals previously submitted to light, moderate or severe spinal cord injury. Histological analysis of spinal cord segments which enclosed the injured site allowed the evaluation of the injury and the relationship between sensitive and motor lesions.

The purpose of this study was to explore the differences in the aerobic response to wheeling between wheelchair dependent individuals and able-bodied individuals of similar genders and ages. Five wheelchair dependent men (WC) and five able-bodied men (AB) performed a 13 minute wheeling test (5 min. at rest, 8 min. wheeling) at 4.0 km∙hr-1. Heart rate (HR) and VO2 were recorded using a Vmax ST system during the constant speed test. There was no significant difference in HR or VO2 between the two groups during rest. Both HR and VO2 were higher for WC during exercise. The mean METS during exercise for WC and AB were 3.589 ± 0.516 and 2.726 ± 0.164, respectively. The results indicate that at a given workload a spinal cord injured wheelchair user will have a greater aerobic response than an able-bodied person in a wheelchair completing the same task.

Background: Spinal cord injury (SCI) is a devastating condition for which current treatment strategies provide no cure. Delivery of growth factors at the injury site may stimulate endogenous stem cells for nerve regeneration. Biocellulose (BC) was reported to be biocompatible, abundant and have adjustable mechanical properties. However, BC has not been tested for the treatment of SCI. Hypothesis: Composite microsphere loaded BC tubes can have a sustained protein release profile with high encapsulation efficiency and low initial burst rendering it suitable for spinal cord regeneration. Methods: Bovine serum albumin loaded poly (lactic-co-glycolic acid) microspheres were fabricated and characterized while studying the effect of different process parameters on encapsulation efficiency, release profile and morphology. Microspheres were loaded to BC tubes and were characterized morphologically and mechanically. Results: Inner phase volume and the drug:polymer ratio are the main factors impacting microsphere protein encapsulation. Furthermore, presence of different osmotic agent concentrations in the aqueous phase produced a smooth morphology while eliminating the initial burst. Finally, the composite BC tubes were fabricated, and mechanical properties were suitable for SCI applications. Contexte : Les lésions de la moelle épinière sont une maladie dévastatrice que les stratégies de traitement actuelles ne permettent pas de guérir. L'administration de facteurs de croissance sur le site de la lésion peut stimuler les cellules souches endogènes pour la régénération des nerfs. La biocellulose est biocompatible, abondante et possède des propriétés mécaniques ajustables. Cependant, la biocellulose n'a pas été testée pour le traitement des lésions de la moelle épinière. Hypothèse : Les microsphères en composite situées dans les tubes de biocellulose peuvent avoir un profil de libération soutenue de protéines avec une grande efficacité d'encapsulation ainsi qu’un faible taux de libération initial, ce qui les rend appropriés pour la régénération de la moelle épinière. Méthodes : Des microsphères de poly (acide lactique-co-glycolique) chargées d’albumine de sérum bovin ont été fabriquées et caractérisées tout en étudiant l'effet de différents paramètres du processus sur l'efficacité de l'encapsulation, le profil de libération et la morphologie. Les microsphères ont été mises dans des tubes de biocellulose et ont été entièrement caractérisées. Résultats : Le volume de la phase interne et le ratio médicament : polymère sont les principaux facteurs qui influent sur l'encapsulation des protéines en microsphères. De plus, la présence de différentes concentrations de sel dans la phase aqueuse a produit une morphologie lisse tout en éliminant la libération initiale. Enfin, les tubes de biocellulose en composite ont été fabriqués et les propriétés mécaniques étaient adaptées pour l’application sur des lésions de la moelle épinière.

Indiana University-Purdue University Indianapolis (IUPUI) / Spinal cord injury (SCI) is devastating and debilitating, and currently no effective treatments exist. Approximately, 12,000 new cases of SCI occur annually in the United States alone. The central nervous system has very low repair capability after injury, due to the toxic environment in the injured tissue. After spinal cord trauma, ruptured blood vessels cause neighboring cells and tissues to be deprived of oxygen and nutrients, and result in the accumulation of carbon dioxide and waste. New blood vessels form spontaneously after SCI, but then retract as the injured tissue forms a cavity. Thus, the newly formed vasculature likely retracts because it lacks a structural support matrix to extend across the lesion. Currently, in the field of spinal cord injury, combinational treatment approaches appear to hold the greatest therapeutic potential. Therefore, the aim of these studies was to transplant a novel, non-immunogenic, bioengineered hydrogel, into the injured spinal cord to serve as both a structural scaffold (for blood vessels, axons, and astrocytic processes), as well as a functional matrix with a time-controlled release of growth factors (Vascular endothelial growth factor, VEGF; Glial cell line-derived neurotrophic factor, GDNF). The benefit of this hydrogel is that it remains liquid at cooler temperatures, gels to conform to the space surrounding it at body temperature, and was designed to have a similar tensile strength as spinal cord tissue. This is advantageous due to the non-uniformity of lesion cavities following contusive spinal cord injury. Hydrogel alone and combinational treatment groups significantly improved several measures of functional recovery and showed modest histological improvements, yet did not provoke any increased sensitivity to a thermal stimulus. Collectively, these findings suggest that with further investigation, hydrogel along with a combination of growth factors might be a useful therapeutic approach for repairing the injured spinal cord.

Indiana University-Purdue University Indianapolis (IUPUI) / The vascular network highly coordinates with the central nervous system (CNS) on exchanging oxygen, nutrients and information transfer. The resemblance of the two systems at anatomical, cellular, and molecular levels also demonstrates their interdependence. The spinal cord is an integrated part of the CNS. Traumatic spinal cord injury (SCI) causes rapid systemic vascular responses and local neural tissue damage at the initial phase. The early disruption of the spinal vasculature breaks the supply-and-demand balance and facilitates the deterioration of the spinal cord tissue and functional deficits. Therefore, it is important to dissect the mechanism underlying vascular injury-mediated histological and functional consequences in order to develop potential therapeutic strategies. To visualize dynamic vascular changes after an acute SCI, a novel duo-color in vivo imaging technique was successfully developed in adult rats at the cervical level. This technique overcomes previous technical hurdles allowing real-time observation of vascular changes in live animals. Correlated with histological measures, in vivo vascular outcomes revealed a temporospatial relationship with neuronal and axonal loss, myelin disruption, inflammation, and glial responses. For the first time, we defined a “transitional zone” where significant blood vessel dilation and vascular leakage were observed simultaneously with vascular changes occurred at the injury epicenter acutely after SCI. These vascular changes at the transitional zone happened before any other cellular damage after SCI, suggesting a time window to prevent further neuronal damage in this region. Targeting the observed vascular leakage can work as a proof of concept that early vascular dysfunction contributes to the secondary neural tissue damage. Indeed, intravenous delivery of ferulic acid conjugated with glycol chitosan (FA-GC) to the injured sites immediate after SCI resulted in reduced vascular leakage, ventral horn neuronal loss, and partial recovery of forelimb function following a clinically-relevant contusive SCI at the 7th cervical spinal cord level. In conclusion, this work elucidated a novel role and mechanism of early vascular damage in the “transitional zone” prior to the secondary damage of neural tissue in this region and provided a novel treatment strategy for early neuroprotection and functional recovery. / 2021-11-04

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