Indiana University-Purdue University Indianapolis (IUPUI) / Hydrocephalus is a disease characterized by an increase in cerebrospinal fluid (CSF) in the ventricles of the brain. This manifests as a result of either overproduction or underabsorption of CSF leading to increases in pressure, swelling and loss of brain matter. Current treatments for this disease include surgical interventions via the introduction of shunts or endoscopic third ventriculostomy, both of which aim to redirect flow of CSF in to another cavity for absorption. Limited pharmacotherapies are available in the treatment of hydrocephalus, and there exists a clinical need for drug therapies, which can ameliorate the pathophysiology associated with hydrocephalus and ventriculomegaly. CSF is produced primarily by the choroid plexus (CP), found in the ventricles of the brain. Composed of a high resistance epithelium surrounding a capillary network, the CP epithelium acts as a barrier, regulating ion transport between the CSF and blood. Transient Receptor Potential Vanilloid-4 (TRPV4) is a nonselective Ca2+-permeable cation channel expressed in the CP which is being investigated for its role in CSF production. To study hydrocephalus, we utilize two model systems; the TMEM67-/- Wpk rat, and the PCP-R cell line. The Wpk rat model is used to study the effects of drug intervention on the development and progression of hydrocephalus. The PCP-R cell line is utilized for studies which aim to understand the mechanisms by which CSF is produced. Using Ussing chamber electrophysiology, we are able to study the role of specific channels, transporters and modulators in driving epithelial ion flux across the CP. This research aims to establish a role for TRPV4 in production and regulation of CSF, and to interrogate a mechanism by which this ion transport occurs. The chapters that follow describe components of the pathway by which TRPV4 is activated and ion flux is stimulated.

The purpose of this study was to examine football neck collars and determine their effectiveness at preventing transient brachial plexopathy and other neck injuries due to football impacts. Transient brachial plexopathy, commonly called a stinger or burner, is an injury to the brachial plexus. As many as 65% of collegiate football players will receive suffer such an injury. Accessory neck collars are worn to mitigate the risk of stingers, although little research has been performed to test their effectiveness. In addition to the standard shoulder pad and helmet combination, three collars were tested: the McDavid Cowboy Collar, a collar designed by a Virginia Tech physician called the Bullock Collar, and a prototype device called the Kerr Collar. This study utilized a Hybrid-III 50th percentile male outfitted with a standard collegiate football helmet and shoulder pads, and impacted with a linear pneumatic impactor. Forty eight total impacts were performed; impacts were performed at side, front, and axial loading impact locations, with low and high speed impacts, and normal and raised shoulder pad configurations. Each collar was effective at some positions, but no collar was effective at all impact locations. The Cowboy Collar reduced lower neck bending moments in the front position, but raised upper neck bending moments. It also reduced lower neck bending moments in the side position, but only in the raised configuration. The Bullock Collar was effective at reducing lower neck bending moment in the side position. The Kerr Collar was effective at reducing lower neck bending moments in the side impact location, and provided a larger percent reduction in impactor force in the axial loading position, compared to the shoulder pads alone. Further testing is needed at lower impact velocities that more closely represent injurious impacts in the field. / Master of Science

臂叢阻滯麻醉可以阻斷同側正中神經，尺神經，橈神經和肌皮神經，故其經常被用於上肢手術中麻醉和/或鎮痛。臂叢阻滯麻醉也可以阻滯同側交感神經，導致同側上肢血管擴張（動脈和靜脈）和血流增加。脈沖多普勒超聲技術可以檢測到這些局部的血流動力學變化。文獻回顧表明迄今為止發表的大部分報道片面地評估了臂叢阻滯麻醉後上肢的局部血流動力學變化缺乏全面而系統的研究，並且報道中關於脈沖多普勒超聲技術用於上肢局部血流動力學測量的可靠性和可重復性的數據也很有限。此外，上肢的局部血流動力學變化是否與測量的位置或者使用的臂叢阻滯麻醉技術有關尚且未知。 / 我假設脈沖多普勒超聲是壹種可靠的測量上肢血流動力學變化的方法，它可以系統地定量測定臂叢阻滯麻醉後上肢的局部血流動力學變化，確定這些變化在上肢不同部位的差異，以及確定不同臂叢阻滯麻醉技術後局部血流動力學變化的差異。以下的部分列舉了本博士課題中開展的壹系列研究來證實我的假設。 / 第壹，我們在12個健康年輕誌願者中（年齡21-34歲）用脈沖多普勒超聲在上肢肱動脈和指掌側總動脈進行血流動力學測量，評估其在觀察者內和觀察者間的差異性。兩個觀察者獨立進行了測量。測量的指標包括收縮期峰值血流速度（厘米/秒），舒張末期血流速度（厘米/秒），收縮期峰值血流速度和舒張末期血流速度比值，平均速度（厘米/秒），時均速度（厘米/秒），阻力指數，搏動指數，動脈直徑（厘米），和血流量（毫升/分鐘）。結果顯示脈沖多普勒超聲是壹種可靠的方法，可用來重復測量上肢的局部血流動力學參數（組內相關系數>0.9）. / 第二，我們在8個病人中（年齡24-70歲）系統地評估了超聲波引導下的腋路臂叢神經阻滯後同側肱動脈的局部血流動力學變化。結果表明臂叢神經阻滯後最早的變化是脈沖多普勒頻譜波形的變化，其波形由三相變為單相，舒張期血流曲線擡升。隨著時間推移，收縮期峰值血流速度，舒張末期血流速度，平均速度，時均速度，動脈直徑，和血流量均顯著增加，收縮期峰值血流速度和舒張末期血流速度比值，阻力指數，搏動指數顯著降低。大部分變化發生在神經阻滯後5分鐘。在所有的局部血流動力學指標中，舒張末期血流速度表現出最顯著的變化（3.7倍），其增加超過收縮期峰值血流速度（1.5倍）和平均速度（2.8倍）。 / 第三，利用15個病人（年齡23-70歲），我們評估了超聲波引導下的鎖骨上臂叢神經阻滯後上肢近端動脈（肱動脈）和遠端動脈（指掌側總動脈）血流動力學變化的差異。臂叢神經阻滯之後，在能量多普勒圖像上，指掌側總動脈表現出更明顯的血管擴張。在脈沖多普勒頻譜波形中，兩個動脈均出現舒張早期的反流消失以及舒張期曲線擡升。另外，收縮期峰值血流速度，舒張末期血流速度，平均速度，時均速度，動脈直徑，和血流量增加，收縮期峰值血流速度和舒張末期血流速度比值，阻力指數，搏動指數顯著降低。這些指標的相對變化在指掌側總動脈比肱動脈更顯著。此研究中，4個病人出現對側手部溫度的增加，以此推測局部麻醉藥的雙側擴散。 / 第四，我們開展了壹項前瞻性隨機對照研究來比較腋路和鎖骨上臂叢神經阻滯引起的局部血流動力學變化的不同。兩組病人人口統計學資料類似。兩種臂叢神經阻滯技術均引起肱動脈和指掌側總動脈收縮期峰值血流速度，舒張末期血流速度，平均速度，時均速度，動脈直徑，和血流量的顯著增加，收縮期峰值血流速度和舒張末期血流速度比值，阻力指數，搏動指數顯著降低。跟腋窩方法相比，鎖骨上技術能夠引起肱動脈時均速度和血流量更顯著的增加。然而，在感覺神經阻滯起效方面，腋窩方法比鎖骨上方法更快。 / 總之，脈沖多普勒超聲可重復地測量肱動脈和指掌側總動脈的血流動力學參數及其變化。臂叢阻滯麻醉引起肱動脈和指掌側總動脈脈沖多普勒頻譜形態的變化，血流速度的增加和血流量的增加。這些局部血流動力學變化在指掌側總動脈中比肱動脈更顯著。鎖骨上臂叢神經阻滯比腋窩方法引起更顯著的局部血流動力學變化。臨床醫生可以利用上肢遠端動脈的局部血流動力學變化來評價臂叢阻滯麻醉的交感神經阻滯效應。麻醉醫師還可以根據這些發現為術後需要較好血流灌註的上肢血管手術選取臂叢神經阻滯方法。 / Brachial plexus block (BPB), which produces sensory and motor blockade of the ipsilateral median, ulnar, radial and musculocutaneous nerves, is frequently used for anesthesia and/or analgesia during surgical procedures of the upper extremity. BPB also produces ipsilateral sympathetic nerve blockade that is characterized by vasodilatation (venous and arterial), and an increase in blood flow to the ipsilateral upper extremity. Pulsed wave Doppler (PWD) ultrasound (US) has been used to evaluate these regional hemodynamic changes. A review of the literature shows that most published reports to date have only partially evaluated the regional hemodynamic changes in the upper extremity after a BPB. There are also limited data demonstrating that PWD US is a reliable or reproducible method of quantifying the regional hemodynamic changes in the upper extremity. Moreover, it is also not known whether the regional hemodynamic changes vary with the site of measurement or the technique of BPB used. / I hypothesized that PWD US is a reliable method for measuring regional hemodynamic parameters in the upper extremity. It can be used to comprehensively quantify the regional hemodynamic changes after a BPB and to determine the extent of these changes at different sites in the upper extremity and after different techniques for BPB. The following section outlines a series of studies that I undertook during this PhD project to corroborate my hypothesis. / Firstly, we sought to assess the intra-observer and inter-observer variability of measuring regional hemodynamic parameters, in the brachial and common palmar digital arteries of the upper extremity, using PWD US in 12 healthy young volunteers aged 21-34 yrs. The measurements were performed independently by two observers. Measured hemodynamic parameters included peak systolic velocity (PSV, cm/s), end diastolic velocity (EDV, cm/s), ratio of PSV and EDV (S/D), mean velocity (Vmean, cm/s), time-averaged mean velocity (TAVM, cm/s), resistance index (RI), pulsatility index (PI), the arterial diameter (d, cm), and blood flow (mL/min). The results showed that PWD US is a reliable and reproducible method of measuring regional hemodynamic parameters in the upper extremity (ICC>0.9). / Secondly, we comprehensively evaluated the regional hemodynamic changes in the ipsilateral brachial artery after an ultrasound guided (USG) axillary BPB in eight adult patients aged 24-70 yrs. Our results suggested that the earliest change after the BPB was a change in the morphology of the PWD spectral waveform from a triphasic to a monophasic waveform and an elevation in the diastolic blood flow velocity. Over time, there was also a significant increase in PSV, EDV, Vmean, TAVM, d, and blood flow, and a decrease in S/D ratio, RI, and PI. Most of these changes were seen as early as 5 minutes after the block. The increase in EDV (3.7-fold) was the most notable change, and it was significantly greater than the increase in PSV (1.5-fold) and Vmean (2.8-fold). / Thirdly, the regional hemodynamic changes in the proximal (brachial artery) and distal (common palmar digital artery) artery of the upper extremity after an USG supraclavicular BPB was investigated in 15 adult patients aged 23-70 yrs. After the block, the common palmar digital artery showed more obvious vasodilatation on the power Doppler US scan. In the PWD spectral waveform, and in both arteries studied, the protodiastolic blood flow disappeared and there was an elevation of the diastolic curve. Also there was a significant increase in PSV, EDV, Vmean, TAVM, d, and blood flow, and a significant reduction in S/D ratio, PI and RI in both arteries. Relative changes of these parameters were greater in the common palmar digital artery than in the brachial artery. In this study, bilateral spread of local anesthetic was observed in 4 patients, as evidenced by an increase of skin temperature on the contralateral hand. / Fourthly, a prospective and randomized study was conducted to compare the regional hemodynamic changes in the upper extremity after an axillary and supraclavicular BPB. The two study groups were similar with respect to demographic data. Both axillary and supraclavicular BPB caused a significant increase in PSV, EDV, Vmean, TAVM, d, and blood flow, and a significant reduction in S/D ratio, PI and RI in both the brachial and common palmar digital arteries. Compared with the axillary approach, the supraclavicular approach produced significantly greater increases in TAVM and blood flow in the brachial artery. However, the onset of sensory blockade was faster after the axillary BPB than with the supraclavicular BPB. / In conclusion, PWD US is a reliable and reproducible method for quantifying the regional hemodynamic parameters in both the brachial and common palmar digital arteries. BPB produces a change in the morphology of the PWD spectral waveform, arterial vasodilatation, an increase in blood flow velocity, and an increase in blood flow in both the ipsilateral brachial and common palmar digital arteries. These changes in regional hemodynamic parameters were more profound in the common palmar digital artery than in the brachial artery. Also these changes were more significant after a supraclavicular BPB than after an axillary BPB. These findings will allow clinicians to evaluate the sympathetic effect of a BPB using regional hemodynamic changes in the distal arteries of the upper extremity. These findings will also allow anesthesiologists to make an evidence-based choice on the techniques of BPB for vascular surgery of the upper extremity when good tissue perfusion is desirable postoperatively. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Jiawei. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 182-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / TABLE OF CONTENTS / ABSTRACT / 中文摘要 / STATEMENT OF WORK / ACKNOWLEDGMENTS / PUBLICATIONS AND PRESENTATIONS / LIST OF ABBREVIATIONS / LIST OF TABLES / LIST OF FIGURES / Chapter CHAPTER 1 --- Introduction / Chapter 1.1 --- Introduction / Chapter 1.2 --- Aims of the project / Chapter 1.3 --- Outline of the thesis / Chapter CHAPTER 2 --- Literature Review / Chapter 2.1 --- Introduction / Chapter 2.2 --- Why regional hemodynamic changes occur after a BPB / Chapter 2.2.1 --- Anatomy of the sympathetic nervous system in the upper extremity / Chapter 2.2.2 --- The anatomic relationship between the sympathetic nerves and the brachial plexus / Chapter 2.2.3 --- Sympathetic efferents to blood vessels in the upper extremity / Chapter 2.3 --- Methods used to measure regional hemodynamic changes / Chapter 2.3.1 --- Skin and muscle blood flow / Chapter 2.3.2 --- Regional hemodynamic measurements using PWD US / Chapter 2.3.2.1 --- Basics of Doppler ultrasound / Chapter 2.3.2.2 --- Principles of blood flow / Chapter 2.3.2.3 --- Spectral analysis of blood flow using PWD US / Chapter 2.4 --- Published data on regional hemodynamic changes after BPB / Chapter 2.4.1 --- Skin temperature / Chapter 2.4.2 --- Cutaneous and muscular blood flow / Chapter 2.4.3 --- Regional hemodynamic measurements on major arterial branches of the upper extremity / Chapter 2.5 --- Introduction of BPB / Chapter 2.5.1 --- Anatomy of the brachial plexus / Chapter 2.5.2 --- Techniques for performing BPB / Chapter 2.5.3 --- USG BPB / Chapter 2.5.3.1 --- History / Chapter 2.5.3.2 --- Advantages of ultrasound guidance for peripheral nerve blockade / Chapter CHAPTER 3 --- Methodology / Chapter 3.1 --- Introduction / Chapter 3.2 --- Patient preparations / Chapter 3.3 --- Regional hemodynamic measurement / Chapter 3.3.1 --- Ultrasound equipment / Chapter 3.3.2 --- Patient position / Chapter 3.3.3 --- Regional hemodynamic measurements using PWD US / Chapter 3.3.3.1 --- Optimizing settings for B-Mode US / Chapter 3.3.3.2 --- Optimizing settings for PWD US / Chapter 3.3.3.3 --- Measurement of regional hemodynamic parameters / Chapter 3.3.4 --- Measurement of diameter (d) and blood flow (Q) / Chapter 3.4 --- USG BPB / Chapter 3.4.1 --- USG axillary BPB / Chapter 3.4.1.1 --- Scout scan / Chapter 3.4.1.2 --- Aseptic precautions / Chapter 3.4.1.3 --- USG axillary BPB / Chapter 3.4.2 --- USG supraclavicular BPB / Chapter 3.4.2.1 --- Scout scan / Chapter 3.4.2.2 --- Aseptic precautions / Chapter 3.4.2.3 --- USG supraclavicular BPB / Chapter 3.5 --- Outcome data after the BPB / Chapter CHAPTER 4 --- Measurement of Regional Hemodynamic Parameters in the Upper Extremity Using Pulsed Wave Doppler Ultrasound: A Reliability Study / Chapter 4.1 --- Introduction / Chapter 4.2 --- Methods / Chapter 4.2.1 --- Subjects / Chapter 4.2.2 --- Study design / Chapter 4.2.3 --- Data acquisition / Chapter 4.2.4 --- Statistical analysis / Chapter 4.3 --- Results / Chapter 4.4 --- Discussion / Chapter 4.4.1 --- Summary of main findings / Chapter 4.4.2 --- Compared with previous studies / Chapter 4.4.3 --- Sources of measurement variability / Chapter 4.4.4 --- Explanation for the variation in the changes in various regional hemodynamic parameters / Chapter 4.5 --- Conclusion / Chapter CHAPTER 5 --- Regional Hemodynamic Changes after an Axillary BPB: A Pulsed Wave Doppler Ultrasound Study / Chapter 5.1 --- Introduction / Chapter 5.2 --- Methods / Chapter 5.2.1 --- Patient enrollment / Chapter 5.2.2 --- Patient preparation / Chapter 5.2.3 --- Measurement of baseline regional hemodynamic parameters / Chapter 5.2.4 --- USG axillary BPB / Chapter 5.2.5 --- Outcome data after the BPB / Chapter 5.2.6 --- Sensory and motor assessments after the BPB / Chapter 5.2.7 --- Statistical Analysis / Chapter 5.3 --- Results / Chapter 5.4 --- Discussion / Chapter 5.4.1 --- Summary of main findings / Chapter 5.4.2 --- Limitations / Chapter 5.4.3 --- Changes in PWD spectral waveform / Chapter 5.4.4 --- Changes in regional hemodynamic parameters / Chapter 5.4.5 --- Increase in skin temperature / Chapter 5.4.6 --- Effects of local anesthetic / Chapter 5.5 --- Conclusion / Chapter CHAPTER 6 --- Does a Supraclavicular Brachial Plexus Block Induce Comparable Hemodynamic Changes in the Proximal and Distal Arteries of the Upper Extremity? / Chapter 6.1 --- Introduction / Chapter 6.2 --- Methods / Chapter 6.2.1 --- Patient recruitment / Chapter 6.2.2 --- Patient preparation / Chapter 6.2.3 --- Measurement of baseline regional hemodynamic parameters, arterial diameter and blood flow / Chapter 6.2.4 --- USG supraclavicular BPB / Chapter 6.2.5 --- Outcome measurements after the BPB / Chapter 6.2.6 --- Statistical analysis / Chapter 6.3 --- Results / Chapter 6.4 --- Discussion / Chapter 6.4.1 --- Summary of the main findings / Chapter 6.4.2 --- Limitations / Chapter 6.4.3 --- Changes in the PWD spectral waveform / Chapter 6.4.4 --- Explanation of the differences in regional hemodynamic changes in the distal and proximal arteries after BPB / Chapter 6.4.5 --- Increase in skin temperature and its relation to blood flow / Chapter 6.4.6 --- Bilateral sympathetic effect after supraclavicular BPB / Chapter 6.4.7 --- Other findings of this study / Chapter 6.5 --- Conclusion / Chapter CHAPTER 7 --- Does a Supraclavicular Brachial Plexus Block Induce Greater Changes in Regional Hemodynamics than an Axillary Brachial Plexus Block? / Chapter 7.1 --- Introduction / Chapter 7.2 --- Methods / Chapter 7.2.1 --- Sample size estimation / Chapter 7.2.2 --- Exclusion criteria / Chapter 7.2.3 --- Randomized allocation / Chapter 7.2.4 --- Preparations before the ultrasound scan / Chapter 7.2.5 --- Measurement of baseline regional hemodynamic parameters, diameter and blood / Chapter 7.2.6 --- USG axillary and supraclavicular BPB / Chapter 7.2.7 --- Outcome measurements after the BPB / Chapter 7.2.8 --- Statistical analysis / Chapter 7.3 --- Results / Chapter 7.4 --- Discussion / Chapter 7.4.1 --- Summary of the main findings / Chapter 7.4.2 --- Limitations / Chapter 7.4.3 --- Change in the PWD spectral waveform / Chapter 7.4.4 --- Differences in regional hemodynamic changes between the 2 study groups / Chapter 7.4.5 --- Differences in sensory and motor blockade between the 2 study groups / Chapter 7.4.6 --- Changes in skin temperature / Chapter 7.5 --- Conclusion / Chapter CHAPTER 8 --- Summary and Conclusions / APPENDIX / REFERENCES

The thesis topic is "The influence of the early therapy by reflex locomotion according to Vojta on children with brachial plexus palsy postpartum and its social impact from the perspective of their parents."The brachial plexus (BP) consists of nerve bundles based on radicular segments C5-Th1. Innervate muscles girdle blades, shoulder, arm and hand. When BP is damaged the mobility may be impaired (paresis to plegia of muscles), sensation (hypoesthesia to anesthesia, paresthesia, pain) and vegetative symptoms can appear (discoloration and skin temperature changes, changes in hair, nail brittleness). Types of BP palsy are classified according to clinical and anatomic course. Paresis of upper type (Erb-Duchene) is the most common and has the best prognosis, clinically manifest by the adduction and internal rotation of the upper limb, the elbow in extension, the wrist in flexion,the limb is poor, the gripping reflex present. During the paralysis of the lower type (Déjerine-Klumpke) the wrist flexion is not possible and the hand grip is poor or absent, and when there is a disruption of the cervical sympathetic the Horner's syndrome appears. An isolated paresis of the secondary trunk with disabilities muscles innervated n. Radialis is rare. During the complete lesion BP the whole limb is plegic with anesthesia all dermatomes excluding the inner arm. The complete lesion BP has the worst prognosis. BP perinatal injury arises in connection with childbirth. Despite the knowledge of risk factors we fail to prevent these injuries. With all children with postnatal paresis BP the initiation of conservative treatment is indicated, some children require neurosurgery. With some children a residual limb dysfunction remains after the treatment. Among the consequences we include permanent residual paresis, postural abnormalities, limb bone deformities, contractures of joints, shortened arm. Delays in mental development and cognitive impairment are related to motor disorders. The early and quality diagnosis and the immediate initiation of therapy is the prerequisite for successful treatment. The therapy should prevent the development of pathological patterns of movement and evoke and restore optimum momentum. The main aim is the restoration of innervation and hand function and the second one is the elbow flexion and the third is the arm abduction. Vojta method of reflex locomotion is one of the methods used for conservative treatment of peripheral paresis. In therapy, congenital partial patterns of forward movement global models, which is reflective crawling and reflective rotation, are activated. These patterns are inborn but with children with locomotor disorders these are blocked. By repeated targeted activation we can achieve the correct fixation of the correct models and thus enable their use in spontaneous motor fluctuations and pathological compensatory movements are displaced. Reflex locomotion favorably influences other functions such as posture and its management, neurological status, the development of mental and autonomic functions, and oculomotoric and disproportionate growth. The goal of the treatment is to reduce the disability degree and to minimize the future disability and handicap. Improving the quality of the child´s life leads to improvement of the life quality for the entire family. The theoretical part is devoted to BP palsy therapy and reflex locomotion according to Vojta. First, the function of peripheral nervous system is characterised, the other part is devoted to BP injury - mechanisms of injury, diagnosis, treatment options, BP perinatal injuries and rehabilitation of patients with spinal BP. The chapter dealing with Vojta describes the basic principles of Vojta method - reflexive crawling and reflexive rotation. The final chapter deals with the birth of a handicapped child, the need to support families and individuals affected especially in the psychological and sociological levels.

Le vieillissement et la dégénérescence du cerveau, associés à des déficits cognitifs, comportementaux et neurologiques, représentent aujourd'hui un problème majeur de santé publique. L'une des principales maladies liées à l'âge est la maladie d'Alzheimer (MA). L'une des caractéristiques de la MA est l'apparition de plaques amyloïdes, résultant de l'agrégation du peptide ßA4. Physiologiquement, le précurseur de la protéine amyloïde (APP) est clivé par une alpha-sécrétase qui génère un fragment soluble de l'APP (sAPP), important pour la formation de nouvelles cellules nerveuses (neurogenèse). Ce clivage en prévient deux autres, par les béta- et gamma-sécrétases, impliqués dans la MA, et conduisant à la formation du ßA4 toxique. Une analyse du plexus choroïde (PCh) a mis en évidence la forte expression de l’APP par cette structure cérébrale. Le PCh est une structure facilement accessible et produisant le liquide cérébro-spinal : son impact peut donc être répercuté à l’ensemble du cerveau. Il pourrait être une source cérébrale importante d’APP, et contribuer fortement à la pathologie. Mon projet de thèse s'inscrivait dans la possibilité de réguler génétiquement l'expression des formes sauvages et mutées de l'APP au niveau de cette source, et suivre les conséquences sur la neurogenèse adulte et la formation des plaques amyloïdes, marqueur histopathologique de la MA. Par l’utilisation de la thérapie génique pour moduler l’expression de l’APP dans les PCh, nous avons confirmé l’importance de l’APP soluble provenant des PCh dans la neurogenèse adulte. Les PCh semble être une source importante d’APP dans le cerveau, et pourraient avoir un rôle clé dans la maladie d’Alzheimer. / Aging and degeneration of the brain with cognitive decline and neurologic symptoms are major individual and societal problems. The major age-related brain degeneration disease is Alzheimer’s disease (AD) with about 40 million people affected in 2015.Physiologically, the Amyloid Precursor Protein (APP) is cleaved by an alpha-secretase, releasing soluble APP (sAPP) an important regulator of adult neurogenesis. This cleavage prevents two others in positions beta and gamma that generate the ßA4 toxic peptide, a hallmark of Alzheimer Disease.Next generation RNA-sequencing has revealed that APP is the 16th most expressed genes in the choroid plexus (CP), suggesting that it may be a major source of sAPP and ßA4 in the cerebrospinal fluid (CSF). If so, adult neurogenesis in the SVZ and hippocampus may be regulated by the choroid plexus and impeded in mutations favoring ßA4 production. My thesis project fell under the possibility to regulate App expression in the CP, and follow consequences on adult neurogenesis and plaques formation in AD. Using viral vectors to modulate App expression in the CP, we confirmed the importance of sAPP coming from CP in adult neurogenesis. With so, CP seems to be an important source of APPin the brain, and could have a key role in AD.

In this study I reviewed 28 patients with brachial plexus lesions caused by shoulder dislocation. As far as can be established, this is the largest series reviewed in the literature to date. Contrary to most other reports, the neurological lesions involved the supraclavicular as well as the infraclavicular brachial plexus. The only part of the supraclavicular brachial plexus affected was the suprascapular nerve, and this always recovered spontaneously. Isolated axillary nerve lesions were found to have the poorest prognosis for spontaneous nerve recovery. All lesions that showed no recovery after 3 - 5 months were explored and had either a graft or a neurolysis. This study discusses the combinations of nerve lesions, their recovery and the indications for surgical intervention. I also suggest a classification perhaps more clinically relevant than the anatomical classification of Leffert and Seddon (1965).

In dieser Studie wurde Prilocain, ein kurz- bis mittellangwirksames Lokalanästhetikum, mit einem der beiden langwirksamen Lokalanästhetika, Ropivacain bzw. Bupivacain kombiniert, mit dem Zweck ein neues Wirkprofil zu erhalten. Dazu wurden 120 Patienten, die sich einem handchirurgischen Eingriff in axillärer Plexusanästhesie unterzogen, randomisiert und doppelblind einer der vier Behandlungsgruppen zugeteilt: Gruppe PB erhielt 7 mg/kg KG Prilocain 1% + 0,75 mg/kg KG Bupivacain 0,5%, Gruppe PR 7 mg/kg KG Prilocain1% + 0,75 mg/kg KG Ropivacain 0,5%. Gruppe P erhielt 7 mg/kg KG Prilocain 1%, Gruppe R 3 mg/kg KG Ropivacain 0,5%. Entsprechend der Randomisierungsliste wurden die Lokalanästhetika unter kontinuierlicher Nervenstimulation in die Gefäß- Nervenscheide des Plexus brachialis eingebracht. Nach Plexusanlage wurden Sensibilität, Motorik und Temperaturempfinden in den 3 Hautarealen des N. medianus, radialis und ulnaris alle 5 Minuten bis zum Operationsbeginn, postoperativ alle 15 Minuten bis zur vollständigen Rückkehr aller Sinnesqualitäten überprüft. Der Zeitpunkt für das postoperative Auftreten von Schmerzen sowie der Zeitpunkt einer Schmerzmitteleinnahme wurden notiert. Die aktuelle Schmerzstärke wurde postoperativ alle 30 Minuten mittels einer Kategorialskala ermittelt. Die Austestung der Analgesie erfolgte sowohl prä- als auch postoperativ gesondert für jeden Hauptnerven mittels pin-prick Methode. Analog dazu wurde die motorische Blockade unter Berücksichtigung der jeweiligen Kennmuskeln überprüft. Zur statistischen Auswertung fand der Kruskal- Wallis Test und der U- Test von Mann und Withney Anwendung, nominale Variablen wurden mit dem Chi- Quadrat Test überprüft. Im Hinblick auf die Dauer der Anästhesie lagen die Werte der Gruppe R signifikant“ über denen der anderen 3 Gruppen (p<0,001). Bei der Prilocain- Gruppe ließ die Anästhesie gegenüber Gruppe PR (p=0,003) und Gruppe R (p<0,001) „signifikant“ früher nach. Im Vergleich mit Gruppe PB zeigte sich nur in den Hautarealen des N. medianus (p=0,005) und des N. ulnaris (p=0,002) ein „signifikantes“ Ergebnis, der N. radialis lieferte einen Trendwert (p=0,061). Gruppe PB und PR unterschieden sich in Bezug auf das N. ulnaris- Gebiet nicht (p=0,453), der N. radialis zeigte einen Trend (p=0,065). Das Gebiet des N. medianus blieb bei Gruppe PR „signifikant“ länger anästhesiert als bei Gruppe PB (p=0,033). Die Anästhesie ließ in allen 4 Gruppen zuerst im Gebiet des N. radialis nach, danach folgte der N. medianus, zuletzt der N. ulnaris. Die Analgesiedauer lag bei der Ropivacain- Gruppe in allen 3 Nervenarealen „signifikant“ über der von Gruppe PB, PR und P (p<0,001). Gruppe P erlangte ihr Diskriminierungsvermögen stattdessen „signifikant“ früher als die anderen Gruppen (p<0,001). Gruppe PR zeigte im Vergleich mit Gruppe PB in keinem der 3 Nervenareale einen signifikanten Unterschied. Bei der Ropivacain- Gruppe hielt die motorische Blockade „signifikant“ länger an als bei den anderen Gruppen (p<0,001), die Prilocain- Gruppe dagegen hatte „signifikant“ früher die volle Kontrolle über den Arm als Gruppe PB (p=0,009), PR (p<0,001), und R (p<0,001). Die Werte der Gruppe PB und PR waren nicht unterschiedlich. Bei der Rückkehr des Temperaturempfindens fanden sich dieselben Signifikanzen wie bei der Analgesiedauer und der Dauer der motorischen Blockade. Bei Gruppe R kehrte das Temperaturempfinden „signifikant“ später zurück als bei den anderen 3 Gruppen (p<0,001). Die Prilocain - Gruppe fühlte „signifikant“ vor Gruppe PB (p=0,01), PR (p<0,001) und R (p<0,001) Kälte. Zwischen Gruppe PB und PR fand sich auch hier kein Unterschied. Die Anzahl der Patienten, die ein Schmerzmittel einnahmen, war „nicht signifikant“ unterschiedlich zwischen den Gruppen. Die Dauer der Analgetikafreiheit zeigte nur zwischen Gruppe PB und R einen „signifikanten“ Unterschied (p=0,009), alle anderen Gruppen waren gleich. Es konnte gezeigt werden, dass eine Kombination der Lokalanästhetika Prilocain 1% und Ropivacain 0,5% bei axillärer Plexusblockade die Wirkungsdauer von Anästhesie, Analgesie und motorischer Blockade verlängert, ohne die Anschlagszeit zu verändern. Eine Kombination von Prilocain 1% und Bupivacain 0,5% verhielt sich bezüglich der Anschlagszeit und Wirkungsdauer äquipotent zur o.g. Lokalanästhetikakombination. Im Hinblick auf das geringere kardiotoxische Potential von Ropivacain gegenüber Bupivacain sollte aber der Kombination mit Ropivacain der Vorzug gegeben werden. / In this prospective, controlled double-blind study, prilocaine 1 %, a short-to-medium time acting local anaesthetic, was combined with ropivacaine 0.5 % or Bupivacaine 0.5%, both long time acting local anaesthetics, to find a new active profile. Therefore, 120 patients scheduled for axillary block for elective upper limb surgery were randomly assigned to four groups: 30 patients of each group received either 7 mg/kg prilocaine 1 % (group P), 7 mg/kg prilocaine 1 % + 0.75 mg/kg ropivacaine 0.5 % (group PR), 7 mg/kg prilocaine 1 % + 0.75 mg/kg bupivacaine 0.5 % (group PB) or 3 mg/kg ropivacaine 0.5 % (group R), respectively. The axillary plexus was identified with a nerve stimulator and the local anaesthetics were injected into the perivascular sheath. The main outcome measures were onset time to anaesthesia (every 5 min) and postoperative analgesic duration of sensory and motor block for the median, radial and ulnar nerve(every 15 min). Additionally, return of pain and postoperative analgesic requirements were recorded. Intensity of pain was postoperative determined every 30 min by a verbal rating scale. Analgesia was classified using the pin-prick method, motor block was analysed by the knowledge of the specific segment-indicating muscles. Median duration of sensory and motor block was significantly increased in group R compared to group P, PR and PB (p < 0.001). In contrast, analgesia was significantly decreased in group P compared to group R, PR and PB (p < 0.001). No significant differences of all tested parameters between group PR and PB could be observed. To compare postoperative pain and analgesic requirements, the number of patients, who received postoperative analgesics, didn’t change significantly between the groups, nevertheless there was significance between group R and PB concerning time until administration of analgesic (p < 0.009). A mixture of prilocaine 1 % with ropivacaine 0.5 % or bupivacaine 0.5 %, respectively, prolonged the duration of sensory and motor block without modifying the onset time. In view of the higher cardiotoxic potency of bupivacaine compared to ropivacaine the local anaesthetic mixture prilocaine 1 % with ropivacaine 0.5 % should be preferred.

Com o envelhecimento há aumento da incidência de problemas gastrointestinais relacionados com a motilidade intestinal. A atividade física pode promover mudanças funcionais significantes, atuando como minimizadora dos efeitos deletérios do processo de envelhecimento. O controle das funções gastrointestinais é feito pelo sistema nervoso entérico composto por um conjunto de neurônios intramurais, entretanto, nada se sabe sobre os efeitos da atividade física regular sobre o envelhecimento dos neurônios mioentéricos. Desta forma, o presente estudo teve por objetivo analisar as alterações quantitativas e morfométricas causadas pelo envelhecimento e pela atividade física nos neurônios mioentéricos NADH e NADPH-diaforase positivos do duodeno de ratos de meia idade. E ainda verificar em microscopia de luz e eletrônica de transmissão as possíveis alterações na morfologia e ultraestrutura do plexo, e na espessura da túnica muscular. Para tanto, foram utilizados 45 ratos Wistar distribuídos em três grupos: C (seis meses de idade sedentário), S (doze meses de idade sedentário) e T (doze meses de idade submetidos à atividade física). Os animais do grupo T realizaram atividade física cinco vezes por semana, durante seis meses. Nenhuma alteração morfológica foi encontrada entre os grupos, entretanto verificou-se a membrana basal mais bem delineada e fibras colágenas mais agrupadas nos gânglios dos animais dos grupos C e T em relação aos animais do grupo S. Na análise quantitativa observou-se diminuição dos neurônios NADPH-diaforase positivos com o envelhecimento e com a prática de atividade física. Os neurônios NADH-diaforase positivos diminuíram com o envelhecimento, porém aumentaram com a atividade física (P&gt;0,05). Nenhuma alteração significativa (P&gt;0,05) foi verificada na área do perfil neuronal dos neurônios NADPH e NADH-diaforase positivos com o envelhecimento. Em relação à atividade física, observou-se, somente nos neurônios NADPH-diaforase positivos, diminuição significativa na área do perfil celular. Nenhuma alteração significativa (P&gt;0,05) foi constatada na espessura da camada muscular do duodeno. / With ageing, there is an increase in the incidence of gastrointestinal problems related to intestinal motility. Physical activity may promote significant functional alterations, acting to minimize the deleterious effects of the ageing process. The control of gastrointestinal functions is carried out by the enteric nervous system, composed of a network of intramural neurons. However, nothing is known about the effects of regular physical activity on the ageing of myenteric neurons. Therefore, the object of this study was to analyze the quantitative and morphological alterations caused by ageing and physical activity on the NADH and NADPH-diaphorase positive myenteric neurons in the duodenum of middle-aged rats and, furthermore, to verify, through light and transmission electron microscopy, any alterations in the morphology and ultrastructure of the plexus and the thickness of the muscular tunica. To this end, 45 Wistar rats were divided into three groups: group C (six months old - sedentary), group S (twelve months old - sedentary) and group T (twelve months old - submitted to physical activity). The animals of group T underwent physical activity five times a week for six months. No morphological alteration was found among the groups. However, it was found that the basal membrane had a stronger outline and collagen fibers were more grouped in the ganglia of the animals of groups C and T, compared to those of group S. In the quantitative analysis, a reduction in NADPH-diaphorase positive neurons with ageing and with the practice of physical exercise was observed. There was also a decrease in NADH-diaphorase positive neurons with ageing, although there was a slight increase with physical activity (P>0.05). No significant alteration was observed in the area of the neuronal profiles of the NADPH and NADH-diaphorase positive neurons with ageing (P>0.05). With regards to physical activity, a significant reduction in cellular profile area was only found in the NADPH-diaphorase positive neurons. No significant alteration was found in the thickness of the muscular layer of the duodenum (P>0.05). Key words: Myenteric plexus, ageing, physical activity.

Com o envelhecimento há aumento da incidência de problemas gastrointestinais relacionados com a motilidade intestinal. A atividade física pode promover mudanças funcionais significantes, atuando como minimizadora dos efeitos deletérios do processo de envelhecimento. O controle das funções gastrointestinais é feito pelo sistema nervoso entérico composto por um conjunto de neurônios intramurais, entretanto, nada se sabe sobre os efeitos da atividade física regular sobre o envelhecimento dos neurônios mioentéricos. Desta forma, o presente estudo teve por objetivo analisar as alterações quantitativas e morfométricas causadas pelo envelhecimento e pela atividade física nos neurônios mioentéricos NADH e NADPH-diaforase positivos do duodeno de ratos de meia idade. E ainda verificar em microscopia de luz e eletrônica de transmissão as possíveis alterações na morfologia e ultraestrutura do plexo, e na espessura da túnica muscular. Para tanto, foram utilizados 45 ratos Wistar distribuídos em três grupos: C (seis meses de idade sedentário), S (doze meses de idade sedentário) e T (doze meses de idade submetidos à atividade física). Os animais do grupo T realizaram atividade física cinco vezes por semana, durante seis meses. Nenhuma alteração morfológica foi encontrada entre os grupos, entretanto verificou-se a membrana basal mais bem delineada e fibras colágenas mais agrupadas nos gânglios dos animais dos grupos C e T em relação aos animais do grupo S. Na análise quantitativa observou-se diminuição dos neurônios NADPH-diaforase positivos com o envelhecimento e com a prática de atividade física. Os neurônios NADH-diaforase positivos diminuíram com o envelhecimento, porém aumentaram com a atividade física (P&gt;0,05). Nenhuma alteração significativa (P&gt;0,05) foi verificada na área do perfil neuronal dos neurônios NADPH e NADH-diaforase positivos com o envelhecimento. Em relação à atividade física, observou-se, somente nos neurônios NADPH-diaforase positivos, diminuição significativa na área do perfil celular. Nenhuma alteração significativa (P&gt;0,05) foi constatada na espessura da camada muscular do duodeno. / With ageing, there is an increase in the incidence of gastrointestinal problems related to intestinal motility. Physical activity may promote significant functional alterations, acting to minimize the deleterious effects of the ageing process. The control of gastrointestinal functions is carried out by the enteric nervous system, composed of a network of intramural neurons. However, nothing is known about the effects of regular physical activity on the ageing of myenteric neurons. Therefore, the object of this study was to analyze the quantitative and morphological alterations caused by ageing and physical activity on the NADH and NADPH-diaphorase positive myenteric neurons in the duodenum of middle-aged rats and, furthermore, to verify, through light and transmission electron microscopy, any alterations in the morphology and ultrastructure of the plexus and the thickness of the muscular tunica. To this end, 45 Wistar rats were divided into three groups: group C (six months old - sedentary), group S (twelve months old - sedentary) and group T (twelve months old - submitted to physical activity). The animals of group T underwent physical activity five times a week for six months. No morphological alteration was found among the groups. However, it was found that the basal membrane had a stronger outline and collagen fibers were more grouped in the ganglia of the animals of groups C and T, compared to those of group S. In the quantitative analysis, a reduction in NADPH-diaphorase positive neurons with ageing and with the practice of physical exercise was observed. There was also a decrease in NADH-diaphorase positive neurons with ageing, although there was a slight increase with physical activity (P>0.05). No significant alteration was observed in the area of the neuronal profiles of the NADPH and NADH-diaphorase positive neurons with ageing (P>0.05). With regards to physical activity, a significant reduction in cellular profile area was only found in the NADPH-diaphorase positive neurons. No significant alteration was found in the thickness of the muscular layer of the duodenum (P>0.05). Key words: Myenteric plexus, ageing, physical activity.

Etudier les dynamiques linguistiques d'abord, les fait mieux comprendre entre elles et donne en sus une 'explication' des propriétés 'grammaticales' comme des effets seconds. On ne disjoint pas la statique (aujourd'hui) des dynamiques (demain ?). Les moyens sont l'analogie et la proximalité : certains accès sont proximaux (= économiques), d'autres plus chers. Un modèle précis et opérable de la productivité linguistique comporte :<br />- une statique, le 'plexus', est formée d'inscriptions enchevêtrées, exemplaristes et contextuelles. Entre des termes sans propriétés s'opèrent des 'copositionnements'.<br />- des dynamiques abductives combinent quatre mouvements de base cognitivement fondés. L'analyse d'un énoncé est redéfinie comme un étagement de "structure mappings". <br />La 'productivité systémique' a cours dans des paradigmes pluridimensionnels et est expliquée sans traits syntaxiques (qui sont artefactuels et d'apprenabilité douteuse). Un modèle d'apprentissage prédit les sigmoides qui sont l'empirie générale en acquisition.<br />Les dynamiques sont bien premières et la grammaire seconde.