Il n'existe pas de méthode non invasive validée pour déterminer la valeur absolue de la pression intracrânienne (PIC). Le liquide céphalorachidien (LCS) et le liquide cochléaire sont reliés par l'aqueduc cochléaire. Le but de ce projet est d'utiliser l'absorbance de l'oreille, optimale lorsque les structures vibrantes sont en position de repos, de sorte que les étriers lorsque la pression à l'extérieur de l'oreille (dans le conduit auditif externe -P_cae ) contrarie la PIC par les osselets de l'oreille moyenne. Les sujets ont été testés dans différentes positions d'inclinaison du corps, ce qui augmente la PIC, à l'aide d'un tympanomètre à large bande. 78 oreilles (sujets témoins entre 20 et 30 ans) ont montré que l'absorbance est maximale à toutes les fréquences à P_cae = 0 mmH2O en position début, elle diminue de façon complexe à P_cae zéro, mais à nouveau identique l'absorbance maximale à P_cae = 13 mm H2O ± 7 en position allongée, et 23 mm H2O ± 14 en position Trendelenburg (-30°), en 68 oreilles sur 78. Les 10 oreilles restantes présentaient un dysfonctionnement anatomique. Un modèle physique a été établi à partir d'un modèle d'oreille électromécanique classique, qui reproduit le comportement observé en attribuant à la PIC la cause des changements d'absorbance et en prédisant la capacité du P_cae pour compenser les changements d'absorbance dus à la PIC. De plus, 3 patients traités par un test de perfusion ont été testés, ainsi que 2 patients traités par ponction lombaire. Ces patients ont montré l'effet de la pression positive et négative dans les courbes d'absorbance. La littérature permet d'établir une corrélation entre la PIC absolue (dans chaque position du corps) et l'absorbance, nous pouvons conclure qu'en raison de la géométrie de l'oreille moyenne, la relation d'équilibre entre les valeurs absolues est PIC = 15 x P_cae , où 15 est le rapport des surfaces entre la MT et la platine de l’étrier. Des sujets suivis par une mesure invasive de la PIC seront nécessaires pour la continuation de cette étude. / There is no validated non-invasive method for determining the absolute value of intracranial pressure (ICP). Ear connect cerebrospinal fluid (CSF) and cochlear fluid via cochlear aqueduct. The goal of this project is to use ear absorbance, optimal when the vibrating structures are in resting position, so the stapes when the pressure outside the ear (in the external ear canal -Peec) counteracts the ICP through the middle ear ossicles. Subjects are testing in different tilt body position, which increase ICP, using a tympanometer Wideband. 78 ears of control subjects between 20 and 30 years have shown that the absorbance is maximum at all frequencies at Peec = 0 mmH2O in standing posture, decreases in a complex way at zero Peec, but again identical to the maximum absorbance at Peec = 13 mm H2O ± 7 in supine, and 23 mm H2O ± 14 in Trendelenburg posture (-30 °), this in 68 ears out of 78. The remaining 10 ears had an anatomical dysfunction. A physical model was established from a classical electromechanical ear model, which reproduces the observed behavior by attributing to the ICP the cause of changes in absorbance and predicting the ability for Peec to offset the absorbance changes due to ICP. Furthermore, 3 patients treated with a perfusion test were tested as well as 2 patients treated by a lumbar puncture. These patients showed the effect of positives and negatives pressure in absorbance curves. Literature make possible a correlation between absolute ICP (in every tilt body position) and absorbance, we can conclude that due to the geometry of the middle ear, the equilibrium relationship between absolute values is ICP = 15 x Peec, where 15 is the ratio of the areas between the tympanic membrane and the stape plate. Subjects tested by invasive measurement of ICP will be required for the continuation of this study.

No description available.

This study examined how 22 children with spina bifida and hydrocephalus (SBH) and 22 matched control children with the same vocabulary age (VA) performed on story retelling and story generation tasks. The children were asked to retell two stories of different lengths (Stein and Glenn's Melvin, the Skinny Mouse and The Tiger's Whisker) and generate two stories from different stimuli (wordless picture book and verbal story starter). Analyses were conducted in terms of global narrative organization (story structure), local connection of ideas (cohesion), and productivity (number of words and utterances). Two-way ANOVAs were conducted to analyze how the stories and story tasks (retell versus generation) influenced the two groups' narrative performance. When comparisons were made between the two groups' performances on the individual stories, the children with SBH generally produced shorter and less complex stories than their VA peers. Story-by-group interaction effects showed that the children with SBH produced fewer story grammar elements than their VA peers on the retell stories but not on the generated ones. When comparisons were made between the two groups' performances on the type of task (story retell versus generation), results showed that for story retelling, the children with SBH produced stories that contained fewer words and utterances than their VA peers, significantly fewer story grammar components, and more correct cohesive ties. For the story generation task, the children with SBH produced significantly fewer reactions and total story grammar components. Story-by-group interaction effects showed that the children with SBH produced fewer reactions and total different words than the VA group on the story retell task but not the generation task. The results suggest that children with SBH function differently from their vocabulary age peers in some dimensions of narrative production. When the children with SBH encountered the retelling tasks or the more structured generation story, they tended to produce stories that were shorter than those of their VA peers.

Гидроцефалия – это синдром или симптом нарушения ликвородинамики, вызванный самыми различными заболеваниями. Врожденная гидроцефалия ассоциируется с нарушениями двигательной активности у детей раннего возраста. Целью работы стала оценка влияния разработанной программы физической реабилитации на степень выраженности двигательных нарушений у детей от 6 месяцев до 2 лет с гидроцефалией. В исследовании приняли участие 38 детей с гидроцефалией после оперативной коррекции ликвородинамики. В качестве методов исследования степени выраженности двигательных нарушений использовали шкалу оценки моторных функций GMFCS, шкалу оценки мышечной силы, модифицированную шкалу Ашфорта, ортостатическую устойчивость гемодинамических параметров оценивали при вертикализации. Согласно полученным результатам, предложенная программа физической реабилитации позволила снизить степень выраженности двигательных нарушений, улучшить мышечный тонус, повысить двигательную активность у детей с гидроцефалией. Также результаты апробации программы позволили подтвердить значимость восстановления подвижности мелких суставов и мышцы, а также вертикализации для профилактики осложнений, обусловленных ограничениями двигательной активности у детей с гидроцефалией. / Hydrocephaly is a syndrome or symptom of impaired liquorodynamics caused by a variety of diseases. Congenital hydrocephalus is associated with movement disorders in young children. The aim of the work was to assess the impact of the developed program of physical rehabilitation on the severity of motor disorders in children from 6 months to 2 years old with hydrocephaly. The study involved 38 children with hydrocephaly after surgical correction. As methods for studying the severity of motor disorders, the GMFCS scale for assessing motor functions, the scale for assessing muscle strength, the modified Ashworth scale, and the orthostatic stability of hemodynamic parameters were assessed during verticalization. According to the results obtained, the proposed program of physical rehabilitation allowed to reduce the severity of movement disorders, improve muscle tone, and increase motor activity in children with hydrocephalus. Either, the results of approbation of the program made it possible to confirm the importance of restoring the mobility of small joints and muscles, as well as verticalization for the prevention of complications caused by restrictions on motor activity.

Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a cerebrospinal fluid shunt. It has been suggested that INPH has similar pathophysiological mechanisms as cerebrovascular disease, but the vascular risk factor (VRF) profile of INPH patients has not been assessed using a modern epidemiological approach. The cognitive symptoms of INPH resemble the symptoms of depression, but the prevalence of depression among INPH patients is unknown. In addition, few studies investigate the impact of shunting on the quality of life (QoL), and no study has investigated the impact of comorbidity on QoL in INPH patients. The objective of this dissertation was to present the VRF profile of INPH and to investigate the hypothesis that INPH may be a subgroup of vascular dementia. Additional objectives were to assess the prevalence of depression in INPH patients and to investigate the impact of shunting and comorbidities on QoL in INPH. In the first cohort, the prevalence of possible INPH was assessed through clinical and radiological examinations in patients with a transient ischemic attack (TIA), consecutively admitted to the same hospital during 2006-2008. In the second cohort, VRFs, vascular disease and QoL were analysed in INPH patients consecutively shunted 2008-2010 in five out of six neurosurgical centres in Sweden. Patients remaining after inclusion (n=176, within the age-span 60-85 years and not having dementia) were compared to population-based age- and gender-matched controls (n=368, same inclusion criteria as for the INPH patients). Assessed VRFs were: hypertension, diabetes, obesity, hyperlipidemia, psychosocial factors (stress and depression), smoking, alcohol intake, physical activity and, dietary pattern. Cardiovascular, cerebrovascular and peripheral vascular disease as well as QoL were also assessed. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG and, blood samples. In the first cohort, 4% of the TIA patients had clinically and radiologically verified INPH. In the second cohort, VRFs were overrepresented among the INPH patients compared with the controls. The VRFs independently associated with INPH were: hyperlipidemia (Odds ratio (OR): 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), obesity (OR: 5.4, 95%CI: 2.5-11.8) and, psychosocial factors (OR: 5.3, 95%CI: 3.2-8.9). When adding the VRFs that were overrepresented in INPH, although not independently (physical inactivity and hypertension), these six VRFs accounted for 24% of the INPH cases in the elderly population (population attributable risk %: 24). Depression was overrepresented in shunted INPH patients compared to the controls (46% vs. 13%, p<0.001) and the main predictor for low QoL was a coexisting depression (p<0.001). In conclusion, the results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH and indicate that INPH may be subgroup of vascular dementia. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for quality of life should be included in the work-up of INPH patients. The effect of targeted interventions against modifiable VRFs and anti-depressant treatment in INPH patients should be evaluated. / Idiopatisk normaltryckshydrocefalus (INPH, från engelskans ”idiopathic normal pressure hydrocephalus”) är en neurokirurgiskt behandlingsbar demens. Behandlingen är att operera in en shunt som dränerar cerebrospinalvätska från ventriklarna. Det har föreslagits att INPH skulle kunna orsakas av liknande patofysiologiska mekanismer som vid cerebrovaskulär sjukdom, men den vaskulära riskfaktorprofilen hos INPH-patienter har aldrig undersökts i en modern epidemiologisk studie. De kognitiva symtomen vid INPH påminner om symtomen vid depression, men prevalensen av depression hos INPH-patienter är okänd. Få studier undersöker hur shuntning påverkar livskvalitet och ingen studie har undersökt hur komorbiditet påverkar livskvaliteten vid INPH. Syftet med den här avhandlingen var att undersöka den vaskulära riskfaktorprofilen hos INPH-patienter samt att utforska hypotesen att INPH skulle kunna vara en undergrupp till vaskulär demens. Ytterligare ett syfte med avhandlingen var att undersöka hur många INPH-patienter som har depression samt undersöka hur shunting och komorbiditet påverkar livskvalitet vid INPH. I den första kohorten undersöktes kliniska och radiologiska fynd som tydde på INPH hos de patienter som blivit diagnostiserade med en TIA (från engelskans: transient ischemic attack) 2006-2008 på Norrlands Universitetssjukhus i Umeå. I den andra kohorten undersöktes konsekutivt shuntade INPH-patienter 2008-2010 från fem av sex neurokirurgiska kliniker i Sverige. De patienter som inkluderades i studien (n=176, ålder: 60-85 år, ej dementa) jämfördes med köns- och åldersmatchade kontroller från normalpopulationen (n=368, samma inklusionskriterier som för INPH-patienterna). De riskfaktorer som undersöktes var: hypertension, hyperlipidemi, diabetes, fetma, psykosociala faktorer (stress och depression), rökning, alkohol, fysisk aktivitet och diet. Även kardiovaskulära och cerebrovaskulära sjukdomar undersöktes, liksom perifer vaskulär sjukdom samt livskvalitet. Datainsamling skedde genom frågeformulär, kliniska undersökningar, mätningar, EKG och blodprov. I den första kohorten hade 4% av TIA-patienterna kliniskt och radiologiskt verifierad INPH. I den andra kohorten var vaskulära riskfaktorer överrepresenterade hos INPH-patienterna jämfört med iv normalpopulationen. Hyperlipidemi (OR: 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), fetma (OR: 5.4, 95%CI: 2.5-11.8) och psykosociala faktorer (OR: 5.3, 95%CI: 3.2-8.9) var associerade med INPH oberoende av kön, ålder och de andra riskfaktorerna. Hypertension och fysisk inaktivitet var också associerade med INPH, dock inte oberoende av övriga riskfaktorer. Sammanlagd PAR% (från engelskans: population attributable risk %) för de här sex riskfaktorerna var 24%. INPH-patienterna hade depression i högre utsträckning än kontrollerna (46% vs. 13%, p<0.001), och depression var den viktigaste prediktorn för låg livskvalitet. Resultaten tyder på att vaskulär sjukdom och vaskulära riskfaktorer är involverade i den patofysiologiska mekanismen vid INPH. INPH kan vara en undergrupp till vaskulär demens. En fullständig riskfaktoranalys och screening för depression bör ingå i den preoperativa utvärderingen såväl som i forskning på INPH-patienter, och ett mått på livskvalitet bör införas. Effekten av riktade insatser mot såväl vaskulära riskfaktorer som depression vid INPH bör utvärderas.

A validated model of water transport in the cerebral environment is both an ambitious and timely task; many brain diseases relate to imbalances in water regulation. From tumours to strokes, chronic or acute, transport of fluid in the brain plays a crucial role. The importance and complexity of the brain, together with the range of unmet clinical needs that are connected with this organ,make the current research a high-priority. One of the most paradoxical cerebral conditions, hydrocephalus, serves as an excellent metric for judging the success of anymodel developed. In particular, normal pressure hydrocephalus (NPH) is a paradoxical condition with no known cure and existing treatments display unacceptably high failure rates. NPH is considered to be a disease of old age, and like many such diseases, it is related to a change in the transport of fluid in the cerebral environment. This complex system ranges from organ-level transport to cellular membrane channels such as aquaporins; through integrating it in a novel mathematical framework, we suggest that the underlying logic of treatment methods may be misleading. By modelling the transport of cerebrospinal fluid (CSF) between the ventricular system, cerebral tissue and blood networks, we find that changes to the biophysical properties of the brain (rather than structural changes such as aqueduct obstruction) are capable of producing clinically relevant ventriculomegaly in the absence of any obstruction to CSF flowthrough the ventricular system. Specifically, the combination of increased leakiness and compliance of the capillary bed leads to the development of enlarged ventricles with a normal ventricular pressure, replicating clinical features of the presentation of NPH. These results, while needing experimental validation, imply that treatment methods like shunting, that are focussed on structural manipulation, may continue to fail at unacceptably high rates.

Cerebrospinal fluid (CSF) fills a system of cavities at the centre of the brain, known as ventricles, and the subarachnoid space surrounding the brain and the spinal cord. In addition, CSF is in free communication with the interstitial fluid of the brain tissue. Disturbances in CSF dynamics can lead to diseases that cause severe brain damage or even death. So-called infusion tests are frequently performed in the diagnosis of such diseases. In this type of test, changes in average CSF pressure are related to changes in CSF volume through infusion of known volumes of additional fluid. Traditionally, infusion tests are analysed with single compartment models, which treat all CSF as part of one compartment and balance fluid inflow, outflow and storage through a single ordinary differential equation. Poroelastic models of the brain, on the other hand, have been used to simulate spatial changes with disease, particularly of the ventricle size, on larger time scales of days, weeks or months. Wirth and Sobey (2008) developed a two-fluid poroelastic model of the brain in which CSF pressure pulsations are linked to arterial blood pressure pulsations. In this thesis, this model is developed further and simulation results are compared to clinical data. At first, the functional form of the compliance, which governs the storage of CSF in single compartment models, is examined by comparison of two different compliance models with clinical data. The derivations of a single-fluid and a two-fluid poroelastic model of the brain in spherical symmetry are laid out in detail and some of the parameters are related to the compliance functions considered earlier. The finite element implementation of the two-fluid model is described and finally simulation results of the average CSF pressure response and the pressure pulsations are compared to clinical data.

INTRODUÇÃO: A ventriculomegalia é a malformação congênita de sistema nervoso central (SNC) mais prevalente, e a malformação Dandy Walker (apesar de menos prevalente) é, assim como a ventriculomegalia, uma doença com um importante impacto pré e pós-natal na morbidade e mortalidade fetal. A etiologia dessas patologias é heterogênea e o fator genético está entre as principais causas. A técnica mais usada no período pré-natal para rastreamento genético é o cariótipo por banda G; contudo esta técnica não revela todas as anormalidades genéticas. Portanto, em fetos com alteração morfológica ultrassonográfica detectada e cariotipagem tradicional normal, o estudo molecular pode ser oferecido para uma investigação etiológica e aconselhamento genético. OBJETIVO: Este estudo visa investigar a presença de CNVs (do inglês, copy number variations) utilizando cariotipagem por array em amostras de DNA obtidas de fetos portadores de ventriculomegalia (VM) ou Malformação de Dandy-Walker (MDW), com resultado de cariótipo clássico normal. MÉTODO: Foram selecionadas 29 gestantes com fetos portadores de VM e MDW. Das 29 amostras colhidas, 2 foram excluídas devido PCR positivo para infecções congênitas e outras 3 excluídas devido cariótipo por banda G apresentando anomalias cromossômica. Um total de 24 fetos foram incluídos no estudo, sendo 19 portadores de ventriculomegalia e 5 casos de MDW diagnosticados na ultrassonografia pré-natal. Todos os casos apresentavam cariótipo por banda G normal e PCR negativo para infecções congênitas no líquido amniótico. O DNA fetal foi extraído do cordão umbilical através da cordocentese entre 20 e 34 semanas e foi analisado pelo SNP array. As CNVs encontradas foram comparadas com banco de dados e literatura e posteriormente classificadas patogênicas, significado clínico incerto (VUS; do inglês variation of uncertain clinical significance) ou benignas. RESULTADOS: Nos 5 fetos com MDW a média da idade gestacional do diagnóstico foi de 26,8 semanas (SD 1,78 semanas). Todos os fetos eram do sexo feminino. Encontradas 6 CNVs. Todas consideradas benignas. Nos 19 fetos portadores de VM, a média do diâmetro no nascimento foi de 29,9 mm (DP 15,21mm). A média da idade gestacional do diagnóstico foi de 27 semanas (DP: 3,41 semanas). O sexo masculino representou 57,8% dos casos e o feminino, 42,1%. Foram encontradas 41 CNVs (22 benignas e 16 VUS) além de 15 eventos de perda de heterozigosidade (LOH). Nenhuma CNV foi considerada patogênica. CONCLUSÃO: Foi possível detectar CNVs utilizando cariotipagem por array em 22, dos 24 casos selecionados de VM e MDW; determinar qual a região cromossômica alterada, além de associar essas regiões com genes envolvidos. Os genes envolvidos foram estudados e comparados com o banco de dados. Contudo para correlacionar os achados ultrassonográficos com os achados citogenômicos encontrados ainda necessitamos de mais estudos acumulativos para enriquecer os bancos de dados existentes e melhorar a assistência pré-natal, diagnóstico e prognóstico dos pacientes portadores de ventriculomegalia e malformação Dandy Walker / BACKGROUND: Ventriculomegaly is the most prevalent congenital central nervous system (CNS) anomalies. Dandy Walker malformation (DWM), although lower prevalent, is, like ventriculomegaly, a disease with a significant prenatal and postnatal impact on fetal morbidity and mortality. The etiology of these pathologies is heterogeneous and the genetic factor is among the main causes. The most used technique in the prenatal period for genetic tracing is the K-band karyotype. However, this technique does not reveal all genetic abnormalities. Therefore, in fetuses with detected ultrasound morphological alteration and normal traditional karyotyping, the molecular study may be offered for an etiological investigation and genetic counseling. OBJECTIVE: To investigate copy number variations (CNVs) using a single nucleotide polymorphism (SNP) array and identify changes in chromosomal regions in fetuses with ventriculomegaly (VM). METHOD: Twenty nine pregnant women with fetuses with ventriculomegaly and DWM were selected. Of the 29 samples collected, 2 were excluded due to positive PCR for congenital infections and another 3 excluded due to G-band karyotype presenting chromosomal abnormalities. A total of 24 fetuses were included in the study, 19 of whom had ventriculomegaly and 5 MDW cases diagnosed on prenatal ultrasonography. All cases presented normal G-band karyotype and negative PCR for congenital infections in the amniotic fluid. The fetal DNA was extracted from the umbilical cord by cordocentesis between 20 and 34 weeks and was analyzed by the SNP array. The CNV were compared with databases and literature and then classified into three groups: pathogenic CNVs, CNVs with uncertain clinical significance (VUS) and benign CNVs. RESULTS: In the 5 fetuses with MDW the mean gestational age of the diagnosis was 26.8 weeks (SD 1.78 weeks). All fetuses were female. Found 6 CNVs. All CNVs considered benign. In the 19 fetuses with MV, the mean of the cerebral ventricle diameter at birth was 29.9 mm (SD 15.21 mm). The mean gestational age of the diagnosis was 27 weeks (SD: 3.41 weeks). The male gender represented 57.8% of the cases and female, 42.1%. We found 41 CNVs (22 benign and 16 VUS) in addition to 15 heterozygosity loss (LOH). No CNV was considered pathogenic. CONCLUSION: It was possible to detect CNVs using array in 22 of the 24 selected cases of VM and DWM; determine the altered chromosomal region, and associate these regions with the genes involved. The genes involved were studied and compared to the database. However, to correlate ultrasonographic findings with the cytogenetic anomalies detected, we still need more cumulative studies to enrich existing databases and improve prenatal care, diagnosis and prognosis of patients with VM and DWM

INTRODUÇÃO. Atualmente, o tratamento da hidrocefalia é realizado principalmente através de uma Derivação ventrículo-peritoneal (DVP). Este estudo tem como objetivo descrever a aplicação da derivação ventrículosinusal retrógrada (DVSR) em pacientes com hidrocefalia após o tratamento cirúrgico de mielomeningocele. MÉTODO. Estudo prospectivo, randomizado e controlado. Foram selecionados consecutivamente 9 pacientes com hidrocefalia após correção cirúrgica de mielomeningocele de janeiro de 2010 a janeiro de 2012. Os pacientes foram submetidos à DVSR ou DVP eletiva. Cinco submetidos à DVSR e 4 à DVP, sendo seguidos por 1 ano com realização trimestral de avaliações clínicas, de imagem e aplicação do Doppler transcraniano. RESULTADOS. Os pacientes tratados com DVSR apresentaram desfechos clínicos semelhantes aos do grupo de DVP. O Doppler mostrou melhora significativa quando comparado o pré-operatório com o pós-operatório. O grupo DVSR apresentou perímetro cefálico significativamente maior que o grupo DVP. O desenvolvimento neuropsicomotor, complicações e desfechos centrados nos pacientes não diferiram entre os grupos. CONCLUSÕES. A técnica cirúrgica da derivação ventrículo-sinusal retrógrada é viável; ela é uma opção alternativa para o tratamento de hidrocefalia / INTRODUCTION. Currently, treatment of hydrocephalus is accomplished primarily through a ventricular-peritoneal shunt (VPS). This study aims to describe the application of retrograde ventricle-sinus shunt (RVSS) in patients with hydrocephalus after surgical treatment of myelomeningocele. METHOD. A prospective, randomized and controlled study. We consecutively enrolled 9 patients with hydrocephalus after surgical repair of myelomeningocele from January 2010 to January 2012. These patients underwent elective RVSS or VPS. Five underwent RVSS and 4 underwent VPS. These patients were followed for one year with quarterly clinical and image evaluations and application of transcranial Doppler. RESULTS. Patients treated with RVSS showed clinical outcomes similar to those of VPS group. Doppler showed significant improvement when comparing preoperative to the postoperative period. RVSS group showed significantly higher cephalic perimeter than VPS group. Neuropsychomotor development, complications and subjective outcomes did not differ between groups. CONCLUSIONS. Surgical technique of retrograde ventricle-sinus shunt is viable; it is an alternative option for the treatment of hydrocephalus

<div>Hydrocephalus is a debilitating disease characterized by an increase in cerebrospinal fluid (CSF) in the brain, leading to increases in pressure that can ultimately result in death. Current treatments for hydrocephalus include only invasive brain surgery. Therefore, the need for a pharmaceutical therapy is great. In order to develop a suitable treatment, we first must be able to study the disease and the mechanisms by which it develops. By characterizing appropriate in vivo and in vitro models, we are better able to study this disease. In this thesis, the Wpk rat model and the PCP-R cell line are described as such appropriate models. In addition to suitable models, we also require a target for drug treatment. Transient Receptor Potential Vanilloid 4 (TRPV4) is a non-selective cation ion channel present in the main CSF-producing organ in the brain, the choroid plexus (CP). Preliminary data suggest this channel plays a role in the development of hydrocephalus. In the following work, some of the mechanisms by which TRPV4 functions in the brain are also described, including through calcium-sensitive potassium channels and inflammation. From this research, we are able to achieve a better understanding of the function of TRPV4 and how it can affect the development and progression of hydrocephalus.</div>