Injuries to the central nervous system (CNS) have traumatic consequences such as irreparable disability due to the inability of the CNS to regenerate injured nerve fibres. The aim of the work presented here was to develop a scaffold which potentially provides guidance to axons in the injured spinal cord thus facilitating signal transduction. A poly-(lactic-co-glycolic acid) (PLGA, PLA:PGA ratio of 75:25) flat sheet membrane scaffold was created using phase inversion with N-methyl pyrrolidinone (NMP) as the solvent and water as the non-solvent for immersion precipitation. PLGA flat sheet membranes were exposed to surface treatments including aminolysis, peptide immobilisation and ozonation in order to achieve higher cell attachment of PC12 cells, a cell line which was cloned from a solid pheochromocytoma tumour of white rats, and used as a tool for measurement of regeneration. Cell attachment studies revealed no significant difference in cell attachment between modified and not-modified PLGA flat sheet membranes. However, the absence of foetal calf serum (FCS) resulted in fivefold higher cell attachment compared to medium supplemented with 10% FCS. A second scaffold was produced by electrospinning 10% (w/w) PLGA in a chloroform:methanol (CHCl3:MeOH) mixture in ratio of 3:1 resulting in a nanofibrous scaffold. Optimum settings for electrospinning were found to be 3 ml/h feeding rate, 15kV applied voltage and 11cm collector-to-needle distance. Random and aligned PLGA nanofibres were produced, with a fibre diameter of 530±140nm. PC12 cells attached and differentiated to the nanofibrous scaffold. When exposed to NGF these cells stopped dividing and extended neurites. On random fibres, neurite orientation was random, whereas on aligned fibres 63% of neurites grew with the fibre orientation ±15��ᵒ. After 7 days of exposure to NGF, cells had 1-4 neurites on random fibres, reaching a maximum length of 188μm, whereas on aligned fibres, cells had 1-2 neurites, reaching a maximum length of 400μm. PLGA nanofibres were also investigated as a delivery vehicle for bioactive molecules. For this, poly-L-lysine (PLL) was incorporated into electrospun PLGA nanofibres via emulsion electrospinning. PLGA-PLL nanofibres were significantly larger than PLGA nanofibres having a diameter of 830±190nm. In order to visualise the incorporation of PLL, FITC-PLL was electrospun und the resulting nanofibres fluoresced greed. Attachment of PC12s to PLGA-PLL nanofibres was not significantly different compared to PLGA nanofibres. Aligned PLGA-PLL nanofibres were shown to promote neurite outgrowth of PC12s with resulting neurites of up to twice the length compared to aligned PLGA nanofibres. The results suggest that PLGA nanofibres strongly influences neurite organisation, which is potentially useful for future therapeutic approaches. The work in this thesis has shown that electrospun PLGA nanofibre mats have the potential to be used as scaffolds for spinal cord repair addressing topographical guidance and delivery of bioactive molecules to the site of injury.

Hematopoietic cell populations exhibiting detectable telomerase activity and elongated telomere lengths display strong engraftment survivability in humans during transplants. We investigated telomerase activity and telomere length in umbilical cord blood hematopoietic cell populations obtained from ViaCell Inc. at various intervals of a two-week ex vivo stem cell amplification process. Telomerase activity is increased with time in ViaCell's amplification process, perhaps in response to the removal of differentiated cells and expansion of primitive hematopoietic stem cell populations in tissue culture media containing a mixture of growth factors. Two of ViaCell's cell culture fractions were analyzed for telomere length using a TLA. Our results showed relatively long telomere lengths for day-0 and day-14 cord populations, and that despite an upregulation of telomerase activity in Day-14 samples, a loss of about 2 kb of telomeric DNA occurs. Our data are consistent with a model in which the increase in telomerase activity in day-14 ex vivo amplified cord blood hematopoietic cells relative to fresh cord is sufficient to reduce, but not prevent, telomere shortening caused by cell proliferation. Lastly, we investigated various culture conditions that could potentially upregulate telomerase activity in the Day-14 amplified cells. However none of the treatments tested altered telomerase activity. Our detection of increased telomerase activity and relatively long telomere lengths in ViaCell's Day-14 ex vivo amplified cord blood stem cell fraction provides support for ViaCell's Selective Clonogenic AmplificationTM indicating a high engraftment potential for these cells.

Injuries to the peripheral nervous system rank among the most common causes of chronic neuropathic pain. Afflicting millions of people for months or even years, symptoms of this condition have proven difficult to treat clinically. A thorough understanding of the pathophysiological changes induced by such nerve lesions is essential to the development of more efficient therapeutic options. Peripheral nerve injury induces a robust and tightly regulated innate immune response in the dorsal horn of the spinal cord. The precise molecular mechanisms regulating the spatiotemporal dynamics and functional impact of the response remain incompletely understood. Preclinical evidence suggests mitigating this immune response can have a significant therapeutic benefit in the treatment of neuropathic pain, however these findings have yet to be clinically validated. To elucidate the mechanisms regulating the spinal immune response, we used a mouse model of partial sciatic nerve injury exclusively in male adult (2-3-month-old) mice. The spared nerve injury (SNI) model employed throughout our studies induces robust, persistent neuropathic pain-like behavior. We established a time course for the spinal immune response to SNI and used mRNA extracted from the ipsilateral dorsal horn of lumbar spinal cord segments L4 and L5 to analyze changes in the transcriptome at the peak of the immune reaction 7 days after nerve lesion. We discovered upregulation of multiple elements of the triggering receptor expressed on myeloid cells 2 (Trem2) pathway. Trem2 is considered a regulator of toll-like receptor signaling in innate immune cells. It also promotes microglia-mediated phagocytosis in the central nervous system. Recent work from our lab has established neuronal apoptosis in the ipsilateral dorsal horn after SNI as an essential mechanism leading to the development of chronic neuropathic pain-like behavior. We used TUNEL staining of L4 spinal cord sections to compare the clearance of apoptotic cell profiles in Trem2-/- mice to wild-type littermates and discovered a key role for Trem2 in the clearance of apoptotic cells after SNI. We further used genetic deletion of Trem2 as well as administration of a Trem2 agonist in C57Bl/6 mice to assess the impact of Trem2 signaling on both the spinal immune response and neuropathic pain-like behavior after SNI. Neither removal nor augmentation of Trem2 signaling significantly affected the development of neuropathic pain-like behavior. Utilizing flow cytometry, we also evaluated the cellular composition of the spinal immune response. We found no evidence that monocytes from the peripheral circulation invade the spinal cord after SNI, as has been previously suggested. These findings were corroborated by immunohistochemical analysis of spinal cord sections from transgenic mice that express distinct fluorescent proteins in their monocyte and microglia cell populations. To better understand the different mechanisms modulating the spinal immune response, we further examined several transcriptionally regulated signaling pathways. We achieved the greatest reduction of mechanical allodynia in nerve-lesioned mice treated with a P2x4r antagonist. Surprisingly, the removal of fractalkine (Cx3cl1) signaling, another prominent chemokine signaling pathway in microglia, had no significant impact on either the spinal immune response or mechanical allodynia after SNI. Reducing the number of spinal microglia by blocking Csf1r activation did not prevent the development of mechanical allodynia after SNI either. Our findings reveal a more nuanced concept of microglial activation after nerve injury. The impact on neuropathic pain-like behavior and phagocytosis appear to be regulated by pathways that differ from those controlling immune cell recruitment and global activation. These findings provide a greater understanding of the complex mechanisms governing microglial function and offer new insight into molecular targets essential to the development of more efficient treatment options for neuropathic pain.

Human umbilical cord perivascular cells (HUCPVCs) derived from regions surrounding the umbilical cord vessels represent an attractive cell source for cellular therapies, given their proliferative potential and the accessibility of donor material compared with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). However, these cells remain poorly characterised. Using flow cytometry, HUCPVCs were shown to express conventional MSC markers CD29, CD44, CD73, CD90, CD105, CD146, CD166 and integrins alpha1 to -5, alphaV, alphaVβ3, alphaVβ5, β1 and β3, but not CD14, CD34, CD45, STRO-1 or integrin alphaVβ6. HUCPVC marker profiles were consistent between three donors and at different passage numbers. Immunostaining for smooth muscle cell (SMC) markers; alpha-SMA, SM22alpha and smoothelin revealed that HUCPVCs shared expression of these markers with SMCs. However, in comparison with SMCs, HUCPVCs deposited more extensive fibronectin-rich matrices. When compared with hBM-MSCs, HUCPVCs differentiated along adipogenic and osteogenic lineages more slowly and did not progress to terminal phenotypes. mRNA expression of recently identified mesenchymal progenitor cell markers, ROR2, EPHA2, PLXNA2, CDH13 and CD9, was confirmed in HUCPVCs from two donors. In addition, all these markers (except EPHA2) were detected in the umbilical cord vessel wall cells of three donors, confirming their expression in both cultured HUCPVCs and cells of the primary tissue. To determine the roles of these markers in HUCPVCs, they were depleted individually using siRNA. Knockdown (KD) efficiencies of 90-97% were achieved. CD9 KD cells appeared elongated compared to cells treated with control siRNA, and these cells along with ROR2, EPHA2 and PLXNA2 KD cells exhibited larger cell areas than controls. All KD cells also showed decreased proliferative potential by day 6 compared with control siRNA or lipofectamine treated cells. A decrease in total β1 integrins was detected in the CD9 KD cells. Up-regulation of ROR2 and PLXNA2 mRNA expression was detected in HUCPVCs from two donors, when they underwent osteogenic differentiation. ROR2 and PLXNA2 knockdown resulted in increases in PLXNA2 and ROR2 mRNAs respectively, when cells were cultured in osteogenic medium compared with basal conditions. In addition, each individual knockdown revealed that the KD cells showed trends in increasing RUNX2 mRNA expression after 13-16 days in osteogenic medium. These data suggest that ROR2 and PLXNA2 may co-operate in promoting an osteogenic phenotype. Culturing HUCPVCs on non-mineralised BVSMC-derived matrices had very little impact on their differentiation status. In contrast, when HUCPVCs were cultured on mineralised BVSMC-derived matrices in osteogenic medium, their ability to further deposit mineralised matrix was enhanced by 7 days; no accompanying changes in RUNX2, ROR2 or PLXNA2 mRNA expression were detected. Taken together, early up-regulation of RUNX2, ROR2 and PLXNA2 appears to be important in driving osteogenic differentiation in HUPCVCs, whilst subsequent down-regulation of these markers may be required for mineralisation to occur. HUCPVCs express ROR2, PLXNA2, CDH13 and CD9 in vitro and in situ; these markers have distinct roles in regulating cell proliferation, shape and differentiation which may be regulated via changes in β1 integrins. It is not known why HUCPVCs might differentiate along adipogenic and osteogenic lineages more incompletely than hBM-MSCs. Further comparative characterisation of HUCPVCs and hBM-MSCs is a prerequisite for exploiting their vast clinical potential.

Liu Bao Yi. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 83-104). / Abstracts in English and Chinese. / ABSTRACT --- p.i / ACKNOWLEDGEMENT --- p.v / TABLE OF CONTENTS --- p.vi / LIST OF ABBREVIATIONS --- p.xii / LIST OF FIGURES --- p.xivv / LIST OF TABLES --- p.xv / PUBLICATION RELATED TO THIS THESIS --- p.xvii / Chapter PART 1 --- INTRODUCTION AND LITERATURE RESEARCH / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter CHAPTER 2 --- MECONIUM STAINED LIQUOR --- p.3 / Chapter 2.1 --- AMNIOTIC FLUID --- p.3 / Chapter 2.1.1 --- Function of Amniotic Fluid --- p.3 / Chapter 2.1.2 --- Composition Of Amniotic Fluid --- p.3 / Chapter 2.1.3 --- Regulation Of Amniotic Fluid --- p.4 / Chapter 2.1.4 --- Abnormality Of Amniotic Fluid Volume --- p.4 / Chapter 2.2 --- MECONIUM STAINED LIQUOR --- p.6 / Chapter 2.2.1 --- Formation And Composition Of Meconium --- p.6 / Chapter 2.2.2 --- Peristalsis Of Fetal Gastrointestinal Tract --- p.7 / Chapter 2.2.3 --- Meconium Stained Liquor(MSL) --- p.7 / Chapter 2.2.3.1 --- Maturation Theory --- p.7 / Chapter 2.2.3.2 --- Cord Compression Theory --- p.9 / Chapter 2.2.3.3 --- Fetal Hypoxia Theory --- p.10 / Chapter 2.2.4 --- Fetal Effect Of Meconium In Amniotic Cavity --- p.11 / Chapter 2.2.5 --- Meconium Aspiration Syndrome --- p.12 / Chapter 2.2.6 --- Clinical Significance And Limitation Of Studies --- p.13 / Chapter 2.3 --- Purpose Of Study --- p.14 / Chapter CHAPTER 3 --- OXIDATIVE STRESS AND FETAL HYPOXIA --- p.16 / Chapter 3.1 --- OXIDATIVE STRESS --- p.16 / Chapter 3.2 --- FREE RADICALS --- p.16 / Chapter 3.2.1 --- Sources Of Free Radicals --- p.17 / Chapter 3.2.1.1 --- Biological Source Of Free Radicals --- p.17 / Chapter 3.2.1.2 --- Intracellular Source Of Free Radicals --- p.17 / Chapter 3.2.1.3 --- Composition Of Free Radicals And Reactive Oxygen Species --- p.18 / Chapter 3.2.2 --- Cellular Components At Risk From Free Radicals Damage --- p.20 / Chapter 3.2.2.1 --- Proteins --- p.20 / Chapter 3.2.2.2 --- Nucleic Acids And DNA --- p.21 / Chapter 3.2.2.3 --- Membrane Lipids --- p.21 / Chapter 3.2.3 --- Lipid Peroxidation --- p.21 / Chapter 3.2.3.1 --- Chemical Substances Of Membranes --- p.21 / Chapter 3.2.3.2 --- The Reactions Of Lipid Peroxidation --- p.22 / Chapter 3.2.3.3 --- Lipid Peroxidation In Pregnancy --- p.23 / Chapter 3.2.4 --- Protection Against Lipid Peroxidation --- p.24 / Chapter 3.2.5 --- Isoprostanes --- p.26 / Chapter 3.2.5.1 --- Definition --- p.26 / Chapter 3.2.5.2 --- Formation Of Isoprostanes --- p.26 / Chapter 3.2.5.3 --- Metabolism Of Isoprostanes --- p.27 / Chapter 3.2.5.4 --- Biological Characteristics Of Isoprostanes --- p.29 / Chapter 3.2.5.5 --- Isoprostanes As Mediators Of Oxidantive Stress --- p.29 / Chapter 3.3 --- FETAL HYPOXIA --- p.30 / Chapter 3.3.1 --- Fetal Metabolism And Energy Supply --- p.30 / Chapter 3.3.2 --- Free Radical Generation And Fetal Hypoxia-Reoxygenation --- p.33 / Chapter 3.3.3 --- Fetal Hypoxia And Fetal Brain Injury --- p.34 / Chapter 3.3.4 --- Measurement Of Fetal Hypoxia --- p.35 / Chapter 3.3.4.1 --- Acid-Base Balance --- p.35 / Chapter 3.3.4.2 --- Fetal Heart Rate Monitoring --- p.36 / Chapter 3.3.4.3 --- Apgar scores --- p.37 / Chapter 3.3.4.4 --- Pulse Oximetry --- p.37 / Chapter 3.3.4.5 --- Lipid Peroxides --- p.38 / Chapter CHAPTER 4 --- AMNIOINFUSION --- p.40 / Chapter 4.1 --- AMNIOINFUSION --- p.40 / Chapter 4.2 --- AMNIOINFUSION FOR OLIGOHYDRAMNIOS --- p.40 / Chapter 4.3 --- AMNIOINFUSION FOR MECONIUM STAINED LIQUOR --- p.41 / Chapter 4.4 --- PURPOSE OF THE STUDY --- p.42 / Chapter PART 2 --- CLINICAL PROTOCOLS AND MEASUREMENT OF ISOPROSTANES / Chapter CHAPTER 5 --- CLINICAL PROTOCOLS --- p.43 / Chapter 5.1 --- ETHICS --- p.43 / Chapter 5.2 --- CLINICAL PROTOCOLS --- p.43 / Chapter 5.2.1 --- Artificial Rupture Of Membranes (Amniotomy) --- p.43 / Chapter 5.2.2 --- Classification of Meconium Stained Liquor --- p.44 / Chapter 5.2.3 --- Electronic Fetal Heart Rate Monitoring --- p.44 / Chapter 5.2.4 --- Monitoring The Progress of Labour --- p.44 / Chapter 5.2.5 --- Umbilical Cord Blood Gas Analysis --- p.45 / Chapter 5.2.6 --- Apgar Score --- p.45 / Chapter 5.2.7 --- Meconium Aspiration --- p.46 / Chapter 5.2.8 --- Clinical Outcome --- p.46 / Chapter CHAPTER 6 --- MEASUREMENT OF ISOPROSTANES --- p.50 / Chapter 6.1 --- BLOOD PREPARATION --- p.50 / Chapter 6.2 --- REAGENTS --- p.50 / Chapter 6.3 --- GAS CHROMATOGRAPHY AND MASS SPECTROMETRY (GC-MS) --- p.51 / Chapter 6.4 --- PROCEDURES --- p.51 / Chapter 6.5 --- DATA RELIABILITY --- p.53 / Chapter PART 3 --- RESULTS AND DISCUSSION / Chapter CHAPTER 7 --- MECONIUM STAINED LIQUOR (MSL) DURING LABOUR AND NEONATAL CORD BLOOD 8-IS〇-PGF2α CONCENTRATION --- p.54 / Chapter 7.1 --- OBJECTIVE --- p.54 / Chapter 7.2 --- MATERIALS AND METHOD --- p.55 / Chapter 7.3 --- STATISTICAL ANALYSIS --- p.56 / Chapter 7.4 --- RESULTS --- p.57 / Chapter 7.5 --- DISCUSSION --- p.65 / Chapter 7.6 --- CONCLUSION --- p.67 / Chapter CHAPTER 8 --- EVALUATION OF PROPHYLACTIC AMNIOINFUSION FOR INTRAPARTUM MECONIUM STAINED LIQUOR --- p.69 / Chapter 8.1 --- OBJECTIVE --- p.69 / Chapter 8.2 --- MATERIALS AND METHOD --- p.69 / Chapter 8.2.1 --- Study Group: 226}0ب MSL+AI' --- p.69 / Chapter 8.2.2 --- The Procedure Of Amnioinfusion --- p.70 / Chapter 8.2.3 --- Other Study Group --- p.71 / Chapter 8.3 --- STATISTIC ANALYSIS --- p.71 / Chapter 8.4 --- RESULTS --- p.72 / Chapter 8.4.1 --- Comparison Between The 'MSL+AI' And 'MSL-AI' Groups --- p.72 / Chapter 8.4.2 --- Comparison Between 226}0بMSL+AI'And 'Clear Liquor' Groups --- p.74 / Chapter 8.5 --- DISCUSSION --- p.77 / Chapter 8.6 --- CONCLUSION --- p.79 / Chapter CHAPTER 9 --- COMMENTS AND FUTURE RESEARCH --- p.80 / BIBLIOGRAPHY --- p.83

Qin, Yun. / "April 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 229-254). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The phenomenon of panic is one of the most unedifying experiences to inflict the human condition. It is a globally-recognised problem regularly encountered in psychotherapeutic practice. Whilst it is thought that distressing psychological and social (‘psychosocial’) problems might help account for this experience, the precise role they play - particularly in first onset - remains difficult to fathom. For example, whilst there is evidence to suggest that stress related to an individual’s family and work life, marital circumstances, age and gender appear linked with initial episodes of panic, these and many associated stressors people endure remain largely under-researched. Following an inquiry aim that recognises the social construction of reality, this research offers an insight into my first experience of panic attack (my being both a panic sufferer and psychotherapist). The aim was to identify an ‘invisible cord’ (e.g. a series of causally linked stressful life events) related to my panic. These events are typically thought to be found in the twelve months prior to first onset and hold important clues to an individual’s recovery. Hence my research question was: ‘What sense can be made of the invisible cord of events leading to my first experience of panic attack’? Using analytical autoethnographic methods to guide this research, significant personal events were discovered and are presented here in the findings. The earliest events uncovered would stretch back far longer than twelve months; with a series of five scenarios plotted from childhood to my mid-forties. To ensure that this research remained an exercise in critical thinking, each event was then examined alongside broader psychosocial theory and frameworks; offering a connected analysis of this first attack and contingent factors. A summary follows, ‘pulling together’ aspects of this undertaking and offering implications for practice. For example, having only made visible elements of my stressful cord by means of the analytical methods at my disposal (including use of collage and timelines) I suggest that such tools might routinely help other panic sufferers in retracing their past. Equally, in learning that my (often confused) Christian faith was implicated in this panic, I advance that we, as therapists, must remain vigilant to matters of client spirituality: noting that traditional forms of religious guidance are receding in an increasingly sceptical UK society. The thesis concludes with a personal reflection that aims to facilitate a deeper understanding of my research journey.

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研究目的：脊髓損傷是中樞神經系統的嚴重創傷，致殘率高。脊髓損傷後的再生修復一直是當前醫學的難題。迄今為止，脊髓損傷依然缺乏一種有效地治療方法。既往研究證明，胰島素樣生長因子-1對鼠和兔脊髓損傷有保護作用，為了進一步把這些發現應用到臨床方面，我們採用與人類生理更相近的豬只作為實驗動物，構建與臨床相似的脊髓損傷動物模型，并以此為基礎，系統性研究胰島素樣生長因子-1的脊髓保護作用，評估該治療的功效。 / 研究方法：以運動誘發電位為指導，通過直接壓迫和牽拉造成脊髓損傷。18頭猪只隨機分為3組：胰島素樣生長因子-1治療組、生長激素治療組及生理鹽水對照組。脊髓損傷后1小時、24小時及48小時經鞘內注射給藥。于術後第1天、第3天及第21天收集腦脊液檢測胰島素樣生長因子-1和生長激素濃度。連續21天使用修正的 Tarlov 評分標準對動物的運動功能進行評估。第21天處死動物並取材，檢測脊髓中NeuN, GFAP, caspase-3 的活性，并通過TUNEL染色觀察細胞凋亡情況，比較各組之間有無差別。 / 研究結果：通過這種方法建立的脊髓損傷動物模型穩定可靠，各組之間無明顯差異。鞘內給藥24小時及48小時后，腦脊液中胰島素樣生長因子-1和生長激素濃度明顯升高，術後21天檢測，其濃度恢復至基礎值。胰島素樣生長因子-1治療組的運動功能的恢復優於其它各組。與生理鹽水對照組比較，胰島素樣生長因子-1治療組可以明顯提高脊髓損傷后神經元的存活數量，抑制星形膠質細胞增生，減少細胞凋亡。而生長激素治療組僅抑制星形膠質細胞增生，其它方面與生理鹽水對照組無明顯差別。 / 結論：胰島素樣生長因子-1通過提高神經元存活數量，抑制星形膠質細胞增生，以及減少細胞凋亡促進脊髓損傷的恢復。 / Objective: Spinal cord injury is a devastating condition that leads to long-term disabilities. Currently, there is no effective treatment that minimizes spinal cord damage or enhances neurological recovery. Recent studies in rats or rabbits suggested that neurologic recovery after spinal cord injury could be improved with the administration of neurotropic hormones, such as insulin-like growth factor-1 (IGF-1). In order to apply such bench-side discovery to clinical practice, we conducted a study in a higher animal model, akin to human physiology, to evaluate the effectiveness of intrathecal injections of IGF-1to improve neurological recovery in a porcine model of acute traumatic spinal cord injury. / Methods: Traumatic spinal cord injury model was produced by controlled compression and distraction of the exposed T12 segment of the spinal cord. Eighteen pigs were randomly assigned to receive intrathecal injections of either IGF-1, growth hormone or saline at 1, 24 and 48 hours after spinal cord injury. Locomotor function was assessed daily using the validated modified Tarlov’s scale for 21 days. Spinal cord segments were then harvested and the survival of neurons, reactive astrogliosis and apoptosis were determined using neuronal-specific nuclear protein (NeuN), glial fibrillary acidic protein (GFAP), cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assays. / Results: Intrathecal injections of IGF-1 and growth hormone significantly increase the concentrations of the neurotropic hormones in the cerebrospinal fluid after injury (p < 0.01). These concentrations returned to baseline by 21 days after drug delivery. Motor deficits on the first day after injury were comparable between animals in the treatment and control groups. By the end of the third week, neurologic recovery was better in animals receiving IGF-1 treatment (p < 0.05). Immunohistological and western blot studies of the injured segments of spinal cord showed that treatment with both IGF-1 and growth hormone prevented reactive astrogliosis (p < 0.05) while only IGF-1 improved the survival of mature neurons (p < 0.05). IGF-1 also inhibited apoptosis after spinal cord injury (p < 0.05). / Conclusions: In our clinically relevant model of traumatic spinal cord injury in pigs, intrathecal injection of IGF-1 demonstrated beneficial effects on neurological and histological recovery. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wang, Qinzhou. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 105-122). / Abstract also in Chinese. / Declaration of origination --- p.I / Abstract --- p.II / Acknowledgements --- p.VI / Table of Contents --- p.VIII / List of Tables --- p.XII / List of Figures --- p.XIII / Abbreviations --- p.XVIII / Chapter Part 1 --- Spinal Cord Injury: A Review --- p.1 / Chapter Chapter 1-1 --- Acute Spinal Cord Injury: Epidemiology, Socioeconomic Impact --- p.2 / Chapter 1.1.1 --- Epidemiology of Spinal Cord Injury --- p.2 / Chapter 1.1.2 --- Socioeconomic Impact of Acute Spinal Cord Injury --- p.5 / Chapter Chapter 1-2 --- Mechanisms of Spinal Cord Injury --- p.6 / Chapter Chapter 1-3 --- Putative Treatments for Spinal Cord Injury --- p.8 / Chapter 1.3.1 --- Methylprednisolone --- p.8 / Chapter 1.3.2 --- Stem Cell Therapy --- p.11 / Chapter 1.3.3 --- Riluzole --- p.11 / Chapter 1.3.4 --- Other Pharmacological Therapies for Spinal Cord Injury --- p.12 / Chapter Chapter 1-4 --- Insulin-like Growth Factor-1 for the Treatment of Spinal Cord Injury --- p.13 / Chapter Chapter 1-5 --- Summary --- p.17 / Chapter Part 2 --- Insulin-like Growth Factor-1 and Growth Hormone for Spinal Cord Injury --- p.18 / Chapter Chapter 2-1 --- Hypothesis and Objectives --- p.19 / Chapter Chapter 2-2 --- Establishment of Animal Models for Acute Spinal Cord Injury --- p.22 / Chapter 2.2.1 --- Introduction --- p.22 / Chapter 2.2.2 --- Experimental Animals --- p.22 / Chapter 2.2.3 --- Anesthesia --- p.23 / Chapter 2.2.4 --- Transcranial Electrical Motor Evoked Potential --- p.26 / Chapter 2.2.5 --- Surgery --- p.28 / Chapter 2.2.6 --- Statistics --- p.34 / Chapter 2.2.7 --- Results --- p.34 / Chapter 2.2.8 --- Discussion --- p.38 / Chapter Chapter 2-3 --- Optimal Stimulation Protocols for Transcranial Electrical Motor Evoked Potential. --- p.42 / Chapter 2.3.1 --- Introduction --- p.42 / Chapter 2.3.2 --- Methods --- p.42 / Chapter 2.3.2.1 --- Experimental Animals and Anesthesia --- p.42 / Chapter 2.3.2.2 --- Transcranial Electrical Motor Evoked Potential Recording --- p.44 / Chapter 2.3.2.3 --- Stimulation Protocol --- p.44 / Chapter 2.3.3 --- Analyses --- p.44 / Chapter 2.3.4 --- Results --- p.45 / Chapter 2.3.5 --- Discussion --- p.52 / Chapter Chapter 2-4 --- Evaluation of the Efficacy of Insulin-like Growth Factor-1 and Growth Hormone in a Porcine Model --- p.54 / Chapter 2.4.1 --- Introduction --- p.54 / Chapter 2.4.2 --- Materials and Methods --- p.54 / Chapter 2.4.2.1 --- Study Design --- p.54 / Chapter 2.4.2.2 --- Intrathecal Injection and Collection of Cerebrospinal Fluid --- p.58 / Chapter 2.4.2.3 --- Measurements --- p.58 / Chapter 2.4.2.3.1 --- Clinical Evaluation --- p.58 / Chapter 2.4.2.3.2 --- Biochemical Assessments --- p.58 / Chapter 2.4.2.3.3 --- Spinal Cord Section, Histological and Immunochemical Staining --- p.63 / Chapter 2.4.2.3.4 --- Western Blot --- p.69 / Chapter 2.4.3 --- Statistical Analysis and Sample Size Calculation --- p.72 / Chapter 2.4.3.1 --- General Analysis --- p.72 / Chapter 2.4.3.2 --- Sample Size --- p.72 / Chapter 2.4.4 --- Results --- p.73 / Chapter 2.4.4.1 --- Changes of TceMEP --- p.73 / Chapter 2.4.4.2 --- Motor Deficit after Spinal Cord Injury at Baseline --- p.75 / Chapter 2.4.4.3 --- Insulin-like Growth Factor-1 and Growth Hormone in Cerebrospinal Fluid --- p.77 / Chapter 2.4.4.4 --- Clinical Assessment --- p.80 / Chapter 2.4.4.5 --- Demyelination, Neuron Survival and Astrocyte Reaction --- p.85 / Chapter 2.4.4.6 --- Apoptosis --- p.89 / Chapter 2.4.5 --- Discussion --- p.93 / Chapter 2.4.5.1 --- Principal Findings --- p.93 / Chapter 2.4.5.2 --- Insulin-like Growth Factor-1 and Neuroprotection after Spinal Cord Injury --- p.93 / Chapter 2.4.5.3 --- Growth Hormone and Neuroprotection after Spinal Cord Injury --- p.95 / Chapter 2.4.5.4 --- Strengths and Limitations of Our Study --- p.96 / Chapter 2.4.5.5 --- Summary --- p.97 / Chapter Part 3 --- Summary and Future Directions --- p.99 / Chapter Chapter 3-1 --- Summary --- p.100 / Chapter Chapter 3-2 --- Future Directions --- p.103 / Chapter Part 4 --- References and appendixes --- p.104 / References --- p.105 / Appendixes --- p.123

CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / From the need for a specific instrument to evaluate the quality of life of people with spinal cord injury in the Brazilian language, this study was conducted and had the following objectives: to translate and culturally adapt to Portuguese Ferrans and Powers Quality of Life Index Spinal Cord Injury Version â III and characterise the sample in terms of sociodemographic and clinical aspects. Methodological procedure, in which the authorization from the author was obtained. First, there was a stage of translating with the participation of six translators. Then, there was a cultural adaptation taking into account the opinion of five judges. The pretest sample consisted on 30 patients with spinal cord injury, which were selected from the database of the Center for Research and Consulting in Neurological Nursing, and which also met the criteria for inclusion. Data was collected from August to November of 2013 by the final version in Portuguese called Ãndice de LesÃo Medular e Qualidade De Vida â VersÃo III and a questionnaire with social, demographic and clinical data. The study was approved by the Ethics in Research Committee, under the number: 344.927/2013. An index with 74 items was obtained, it was divided into two parts (satisfaction / importance ), on which some adjustments were made for a better understanding. These adjustments resulted in: the addition of four new pronouns or articles to change the genre; nine exclusions of words or articles; two changes from a word to a term; four additional expressions for the purpose of illustrating; four adjusts in expressions; nine changes of only one word. Therefore, there was 24 modifications. It was observed that, in the criteria of semantics equivalence of the index, ortography was rated as âa very appropriate translationâ by a number greater than 87 % ; vocabulary and grammar, by 86%; idiomatic equivalence was rated by a number higher than 74%; experimental equivalence, higher than 78% and conceptual equivalence, by a number greater than 70%. Statistical analysis on semantic, idiomatic, experimental and conceptual evaluations by kappa showed a slight to moderate conformity between the pairs of analysis, adopting (p &#8804; 0.05). It was concluded that this instrument, after being transculturally adapted, has proved to be appropriate under the semantic , idiomatic, experimental and conceptual views, as well as easy to use to evaluate the quality of life of people with spinal cord injury. The study enabled the expansion of scientific knowledge of nursing, especially for professionals in the neurological field, by making it possible to plan, intercede and evaluate the caring for the special needs of these patients. It is now possible to resort to a technology that takes into account a great number of subjective relationships that are not, generally, observed or disclosed. / A partir da necessidade de um instrumento especÃfico para avaliar a qualidade de vida de pessoas com lesÃo medular no idioma brasileiro, realizou-se este estudo que teve como objetivos: traduzir e adaptar culturalmente para a lÃngua portuguesa Ferrans and Powers Quality of Life Index Spinal Cord Injury Version â III e caracterizar a amostra quanto aos aspectos sociodemogrÃficos e clÃnicos. Estudo do tipo metodolÃgico, no qual obteve-se autorizaÃÃo da autora para utilizaÃÃo do instrumento. Inicialmente procedeu-se a etapa de traduÃÃo com a participaÃÃo de seis tradutores, em seguida a adaptaÃÃo cultural pela confrontaÃÃo de cinco juÃzes. A amostra do prÃ-teste constituiu-se de 30 pacientes com lesÃo medular selecionados a partir do banco de dados disponibilizados pelo NÃcleo de Pesquisa e ExtensÃo em Enfermagem NeurolÃgica, e que atenderam aos critÃrios de inclusÃo. A coleta de dados ocorreu nos meses de agosto a novembro/2013, por meio da utilizaÃÃo da versÃo final traduzida para o portuguÃs denominada de Ãndice de LesÃo Medular e Qualidade De Vida â VersÃo III e um questionÃrio com dados sociodemogrÃficos e clÃnicos. O estudo foi aprovado pelo Comità de Ãtica em Pesquisa, Parecer n 344.927/2013. Obteve-se um Ãndice com 74 itens, divididos em duas partes (satisfaÃÃo / importÃncia), com alguns ajustes para facilitar a compreensÃo, dos quais resultaram em quatro acrÃscimos de pronome ou artigo para variaÃÃo do gÃnero; nove retiradas de uma palavra ou artigo; duas mudanÃas de uma palavra para uma expressÃo; quatro expressÃes adicionais com o intuito de exemplificar; quatro ajustes em expressÃes; nove mudanÃas de apenas uma palavra. Desse modo, obteve-se ao todo 24 modificaÃÃes. Quanto aos critÃrios de equivalÃncia semÃntica do Ãndice observou-se que, em relaÃÃo a ortografia o percentual de itens avaliados como TraduÃÃo Muito Adequada foi superior a 87%, vocabulÃrio e gramÃtica a 86%. Na equivalÃncia idiomÃtica obteve-se valores superior a 74%, na equivalÃncia experimental superior a 78% e na equivalÃncia conceitual superior a 70%. A anÃlise estatÃstica para as avaliaÃÃes semÃntica, idiomÃtica, experimental e conceitual por meio do kappa apontou de ligeira a moderada a concordÃncia das anÃlises entre os pares, ao adotar (p &#8804; 0,05). Conclui-se que este instrumento apÃs ser adaptado transculturalmente demonstrou ser adequado do ponto de vista semÃntico, idiomÃtico, experimental e conceitual, alÃm de fÃcil aplicaÃÃo para avaliar a qualidade de vida de pessoas com lesÃo medular. O estudo possibilitou a ampliaÃÃo do saber cientÃfico da enfermagem, em especial aos profissionais que atuam na Ãrea neurolÃgica, por possibilitar o planejamento, as intervenÃÃes e avaliaÃÃo de cuidados direcionados Ãs necessidades tÃo peculiares destes pacientes, podendo agora recorrer a uma tecnologia que mensura muitas relaÃÃes subjetivas e que nÃo sÃo observadas ou reveladas.