Orientador: Marco Antonio Zanini / Resumo: Neurocisticercose é a doença parasitária mais comum do sistema nervoso central. É causada pela ingestão de ovos de Taenia solium, cujas larvas se instalam nos diversos espaços intracranianos e no parênquima encefálico. Uma de suas principais complicações é a hidrocefalia, que pode estar presente em até 30% dos casos. O tratamento da hidrocefalia na neurocisticercose é mais complexo que nas outras formas de hidrocefalia. As taxas de disfunção de derivação ventricular para o peritônio são altas, bem como as taxas de morbidade e mortalidade associadas. Recentes modelos experimentais de neurocisticercose têm sido estudados com foco na relação entre parasita e hospedeiro. Por outro lado, modelos experimentais de hidrocefalia existem há muito tempo e têm contribuído para o entendimento das lesões no tecido encefálico causadas pelo desbalanço entre produção, circulação e absorção do líquor. O objetivo deste trabalho foi desenvolver um modelo experimental de hidrocefalia induzida por neurocisticercose. Inoculamos cistos de Taenia crassiceps (cestodo análogo ao T. solium) no espaço subaracnóideo de ratos através de punção suboccipital da cisterna magna. Por ressonância magnética observamos dilatação do sistema ventricular e das cisternas basais. Exame microscópico demonstrou lesões estruturais no encéfalo induzidas pela hidrocefalia, bem como infiltrados inflamatórios nos compartimentos liquóricos. Assim, desenvolvemos um modelo que reproduz a hidrocefalia por neurocisticercose humana... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

abstract: BioMEMS has the potential to provide many future tools for life sciences, combined with microfabrication technologies and biomaterials. Especially due to the recent corona 19 epidemic, interest in BioMEMS technology has increased significantly, and the related research has also grown significantly. The field with the highest demand for BioMEMS devices is in the medical field. In particular, the implantable device field is the largest sector where cutting-edge BioMEMS technology is applied along with nanotechnology, artificial intelligence, genetic engineering, etc. However, implantable devices used for brain diseases are still very limited because unlike other parts of human organs, the brain is still unknow area which cannot be completely replaceable.To date, the most commercially used, almost only, implantable device for the brain is a shunt system for the treatment of hydrocephalus. The current cerebrospinal fluid (CSF) shunt treatment yields high failure rates: ~40% within first 2 years and 98% within 10 years. These failures lead to high hospital admission rates and repeated invasive surgical procedures, along with reduced quality of life. New treatments are needed to improve the disease burden associated with hydrocephalus. In this research, the proposed catheter-free, completely-passive miniaturized valve is designed to alleviate hydrocephalus at the originating site of the disorder and diminish failure mechanisms associated with current treatment methods. The valve is composed of hydrogel diaphragm structure and polymer or glass outer frame which are 100% bio-compatible material. The valve aims to be implanted between the sub-arachnoid space and the superior sagittal sinus to regulate the CSF flow substituting for the obstructed arachnoid granulations. A cardiac pacemaker is one of the longest and most widely used implantable devices and the wireless technology is the most widely used with it for easy acquisition of vital signs and rapid disease diagnosis without clinical surgery. But the conventional pacemakers with some wireless technology face some essential complications associated with finite battery life, ultra-vein pacing leads, and risk of infection from device pockets and leads. To solve these problems, wireless cardiac pacemaker operating in fully-passive modality is proposed and demonstrates the promising potential by realizing a prototype and functional evaluating. / Dissertation/Thesis / Doctoral Dissertation Electrical Engineering 2020

Indiana University-Purdue University Indianapolis (IUPUI) / Hydrocephalus affects 1 in 1,000 newborns and nearly 1,000,000 Americans, leading to an increase in intercranial pressure due to the build-up of cerebrospinal fluid. There are numerous complications that arise as a result of hydrocephalus, but this study focuses on optic disc edema. The subarachnoid space surrounding the optic nerve contains cerebrospinal fluid. The cerebrospinal fluid increases in hydrocephalus, putting pressure on the optic nerve. The additional intracranial pressure has been proposed to cause axoplasmic stasis within the retinal ganglion cell axons, leading to axonal damage and retinal ischemia. The purpose of this study was to determine the effects of hydrocephalus on the optic disc and retina in several animal models of hydrocephalus. This study uses two genetic and two injury-induced models of hydrocephalus in addition to immunohistochemistry and histological stains to examine the optic disc, thickness of retinal layers, and numbers of retinal cells. This study serves as preliminary work to help build the case that hydrocephalus causes cell loss in the retina, as well as swelling of the retinal ganglion cell axons, leading to axoplasmic stasis and cell death. / Indefinitely

This study served as a pilot study of cingulate gyrus surface areas and their relation to intelligence in individuals with hydrocephalus. Surface areas of the corpus callosum and cingulate gyrus regions were compared between individuals with early hydrocephalus (n = 9) and controls (n = 7). Subsequently, the surface areas were correlated with full-scale intelligence scores and the verbal and nonverbal discrepancy scores. Corpus collosum surface areas were significantly smaller in participants with hydrocephalus. These areas also robustly correlated with full-scale intelligence scores. Although the cingulate gyrus did not differ significantly between the groups, the cingulate gyrus regions were increasingly divergent the more posterior the region. Additionally, the caudal anterior and the posterior cingulate gyrus regions had only moderate positive correlations with full-scale intelligence scores. Although the participants with hydrocephalus had a significantly lower mean performance IQ compared to verbal IQ, the discrepancy scores did not correlate significantly with any of the regions of interest.

Hydrocephalus is developed when the flow of cerebrospinal fluid is obstructed in the ventricles and a pressure build-up is generated within the brain. Ventricular shunts are used to remove excess fluid from the brain, but these shunts have a common problem of failure due to the shunt being obstructed by the build-up of astrocytes. To address this, two sets of 27 designs of ventricular shunts were identified and analyzed with parameters that could potentially reduce obstruction risks. The performance of these designs was examined using fluid simulations on these two sets of 27 designs. One set explored close-tipped shunt designs, and the other assessed open-tipped ones. Following these simulations, adjustments were made to three design variables of the ventricular catheters - inlet hole size, inner shunt diameter, and inner-segment distance. The goal was to optimize these variables to prevent obstruction, ensuring three key design objectives were met: maintaining wall shear stress, ensuring a balanced inlet and outlet pressure difference, and achieving a uniform flow distribution.

No description available.

The framework for a permanently implantable wireless compliance sensor was developed and validated using laboratory experiments. The proposed sensor would measure the intracranial pressure and fluid volume in the brain and return this information to a monitoring device. The designed sensor received power remotely from the monitoring device negating the need for an implanted power source. Impedance measurement estimation techniques were suggested, studied and applied to the compliance sensing system. A new impedance measurement technique, accounting for multiple variability in the domain, was developed. An extensive simulation environment was designed and used to develop the laboratory experiments and hardware. The laboratory experiments validated the theory and simulation, proving the concept. Future work was suggested including the next step in the design process and possible research directions for subsequent theses.

Acetazolamide (AZA), the only drug approved for treatment of hydrocephalus, is effective in only 25-30% of patients while its effect on fluid flow in the choroid plexus (CP) is unknown. The drug reversibly inhibits Aquaporin 4 (AQP4), the most highly expressed „water pore‟ in the brain, and it is postulated that it reduces cerebrospinal fluid (CSF) production by modulating AQP1 (mostly found in the apical membrane of the CP). In this study, we sought to elucidate the effect of AZA on AQP1 and fluid flow in CP. Primary CP culture from p10 Sprague-Dawley rats and TRCSF-B cell line were grown on Transwell permeable supports, treated with 100µM AZA or 100µM Vinpocetine (previously shown to increase AQP1 levels), and tested by: a) Fluid assays using TRITC-labeled Dextran to assay direction and extent of fluid flow; b) Immunoblot, Immunocytochemistry (ICC), and RT-PCR for AQP1 expression. Immnoblots and ICC analyses showed that AQP1 protein levels decrease in a delayed manner (lowest at 12 hours) with AZA treatment. The reduction in AQP1 protein was transient and preceded by a reduction in mRNA levels (lowest at 6 hours). Transwell fluid assays indicate a shift in fluid flow at 2 hours, prior to the changes in AQP1 mRNA or protein. Alteration of fluid flow by AZA (in both primary culture and TR-CSFB) is similar to Vinpocetine‟s effect in primary culture. Together with druginduced alterations in AQP1 levels, these data suggest independent mechanisms behind fluid flow and AQP1 expression.

A neuropsychological examination is often used in tandem with other measures to confirm the diagnosis of idiopathic Normal Pressure Hydrocephalus (iNPH) and to assess improvement in cognitive functioning after a lumbar puncture test. Improvement in symptoms is thought to predict benefit from installation of a ventriculoperitoneal shunt that redirects CSF from the brain. Although the 72-hour external lumbar drain (ELD) has long been the gold-standard drainage procedure, hospitals are increasingly opting for the high-volume lumbar puncture, during which 50ml of CSF is released over an hour before the patient is tested for improvement in symptoms. The primary aims of this study were to evaluate the changes in cognitive performance produced by the two LP procedures and to compare the results produced by each procedure. In a review of medical records, 40 patients met criteria for inclusion. Cognitive functioning in the 72-hour ELD (n = 10) group was compared to changes in patients in the HVLP group, in terms of baseline level of functioning and post-drain changes. Statistical methods used to determine change included ANOVA and Reliable Change Indices. Dominant-hand Grooved Pegboard Test showed significant change after lumbar puncture, with higher mean change in the 72-hour ELD group. 72-hour ELD patients had a slightly higher rate of Reliable Change than HVLP patients. Cognitive changes were bi-directional in both groups. Results suggest that changes in cognitive functioning after lumbar puncture occur in a minority of patients, regardless of procedure type, and may have low predictive value for VPS benefit.

Hydrocephalus can impact all areas of health, including physical, cognitive, and psychosocial functioning. Etiology can be a major factor in health outcomes, but prior research on psychosocial functioning in hydrocephalus has been with limited etiologies. This study examined psychosocial functioning using the Behavioral Assessment System for Children, Third Edition (BASC-3) and the Hydrocephalus Outcome Questionnaire (HOQ) in children aged 5-17 years old. BASC-3 and HOQ parent report scores were compared between hydrocephalus etiologies. Medical factors (number of CSF diversion procedures, history of seizures, and years with hydrocephalus) and SES factors (family income, parent education, and parent occupational status) were examined as potential predictors for psychosocial outcomes. BASC-3 attention and executive functioning and HOQ social-emotional scales differed between etiologies. Years with hydrocephalus and a history of seizures were significant predictors for some BASC-3 scales and the HOQ social-emotional scale. SES variables did not predict any psychosocial outcomes examined. These results provide evidence that children who have had surgery for their hydrocephalus may be at increased risk of psychosocial difficulties, and that etiology and medical history may be contributing factors.