yes / BACKGROUND AND PURPOSE Aging of the healthy brain is characterized by focal or nonfocal white matter (WM) signal abnormality (SA) changes, which are typically detected as leukoaraiosis (LA). Hypertension is a risk factor for WM lesion formation. This study investigated whether LA might be associated with increased cerebrospinal fluid (CSF) pulsatility linked to arterial hypertension. METHODS A total of 101 individuals without neurologic diseases (53 females and 48 males) aged between 18 and 75 years underwent 3T brain MRI with cine phase contrast imaging for CSF flow estimation, after providing their informed consent. LA was defined as the presence of focal T2 WM SA changes and/or nonfocal uniform areas of signal increase termed dirty appearing white matter (DAWM). Relevant information relating to cardiovascular risk factors was also collected. RESULTS When controlled for age and hypertension, significant partial correlations were observed between: DAWM volume and: net negative flow (r = –.294, P = .014); net positive flow (NPF) (r = .406, P = .001); and peak positive velocity (r = .342, P = .004). Multiple linear regression analysis revealed DAWM volume to be significantly correlated with CSF NPF (P = .019) and hypertension (P = .007), whereas T2 WM SA volume was only significantly correlated with age (P = .002). Combined DAWM and T2 WM SA volumes were significantly related with age (P = .001) and CSF peak negative velocity (P = .041). CONCLUSIONS Rarefaction of WM leading to LA is a multifactorial process, in which formation of DAWM induced by hypertension and increased aqueductal CSF pulsatility, may play a contributory role. These two factors appear to act independently of each other in a process that is independent of age.

Horses that are exposed to Sarcocystis neurona, a causative agent of equine protozoal myeloencephalitis, produce antibodies that are detectable in serum by western blot (WB). A positive test is indicative of exposure to the organism. Positive tests in young horses can be complicated by the presence of maternal antibodies. Passive transfer of maternal antibodies to S. neurona from seropositive mares to their foals was evaluated. Foals were sampled at birth (presuckle), at 24 hours of age (postsuckle), and at monthly intervals. All foals sampled before suckling were seronegative. Thirty-three foals from 33 seropositive mares became seropositive with colostrum ingestion at 24 hours of age, confirming that passive transfer of S. neurona maternal antibodies occurs. Thirty-one of the 33 foals became seronegative by 9 months of age, with a mean seronegative conversion time of 4.2 months. These results indicate that evaluation of exposure to S. neurona by WB analysis of serum may be misleading in young horses. Cerebrospinal fluid (CSF) samples from 15 neonatal (2-8 day) foals were examined for the presence of antibodies to S. neurona by WB analysis. Twelve of 13 foals that were seropositive were also CSF positive, suggesting that maternal antibodies to S. neurona cross the blood-CSF barrier in neonatal foals resulting in a positive CSF WB. Repeat taps were performed on 5 of the foals which showed that the immunoreactivity of the western blot decreases over time. Two of the 5 foals were CSF negative at 83 and 84 days of age, with 1 foal still positive at 90 days, and 2 foals positive at 62 days. These results indicate that maternal antibodies to S. neurona in the CSF can confound WB results in neonatal foals up to several months of age. / Master of Science

The regulation of surface tension (ST) by surfactants plays an important role in the human respiratory system but is largely unexplored in brain homeostasis. The aim of this study was to evaluate changes in ST in relation to surfactant proteins (SPs) in children with intraventricular hemorrhage (IVH). CSF samples from 93 patients were analyzed for ST with a force tensiometer and SP-A-D and -G with ELISA assays. Patients belonged to six groups: (i) IVH before primary intervention (PI), (ii) IVH 4–28 days after PI, (iii) IVH 44–357 days after PI, (iv) hydrocephalus, (v) sepsis and (vi) controls. We found indirect correlations and significant differences in ST and SPs (all p < 0.001; except for SP-C, p = 0.007). Post hoc analyses showed significantly decreased ST in IVH patients before PI compared with patients with hydrocephalus, sepsis or controls (p < 0.001), but it increased in IVH patients over time. All SPs were significantly elevated when comparing IVH patients before PI with controls (all p < 0.001; except for SP-C, p = 0.003). Children suffering from IVH displayed an increase in SPs and a decrease in ST as coping mechanisms to preserve CSF flow. The increase in ST over time could serve as prognostic marker for the healing process.

The regulation of surface tension (ST) by surfactants plays an important role in the human respiratory system but is largely unexplored in brain homeostasis. The aim of this study was to evaluate changes in ST in relation to surfactant proteins (SPs) in children with intraventricular hemorrhage (IVH). CSF samples from 93 patients were analyzed for ST with a force tensiometer and SP-A-D and -G with ELISA assays. Patients belonged to six groups: (i) IVH before primary intervention (PI), (ii) IVH 4–28 days after PI, (iii) IVH 44–357 days after PI, (iv) hydrocephalus, (v) sepsis and (vi) controls. We found indirect correlations and significant differences in ST and SPs (all p < 0.001; except for SP-C, p = 0.007). Post hoc analyses showed significantly decreased ST in IVH patients before PI compared with patients with hydrocephalus, sepsis or controls (p < 0.001), but it increased in IVH patients over time. All SPs were significantly elevated when comparing IVH patients before PI with controls (all p < 0.001; except for SP-C, p = 0.003). Children suffering from IVH displayed an increase in SPs and a decrease in ST as coping mechanisms to preserve CSF flow. The increase in ST over time could serve as prognostic marker for the healing process.:1. Einführung 3 1.1 Intraventrikuläre Hämorrhagie 3 1.1.1 Allgemeiner Überblick 3 1.1.2 Pathogenese 3 1.1.3 Risikofaktoren und Prävention 4 1.1.4 Klinik 5 1.1.5 Komplikationen 6 1.1.6 Behandlungsoptionen bei IVH und PHVD 7 1.1.6.1 Medikamente 7 1.1.6.2 Interventionen 7 1.2 Surfactant und Surfactant-Proteine 8 1.3 Zusammenfassung der IVH-Problematik und Fragestellungen der Dissertation 11 2. Publikationsmanuskript 13 3. Zusammenfassung der Arbeit 28 4. Literaturverzeichnis 32 5. Abkürzungsverzeichnis 39 6. Anlagen der Originalpublikation 41 7. Darstellung des eigenen Beitrags 48 8. Erklärung über die eigenständige Abfassung der Arbeit 49 9. Lebenslauf 50 10. Publikationen 51 11. Danksagung 52

Neurocisticercose (NC) é a doença parasitária mais comum do SNC, representando grave problema de saúde pública em nosso país. O diagnóstico da NC é baseado em dados clínicos e epidemiológicos, reações sorológicas no soro e LCR, além de exames de neuroimagem. A detecção de antígenos de Taenia através de teste de ELISA, mediante a utilização de anticorpos altamente purificados, constitui metodologia recente capaz de informar sobre a vigência de atividade clínica da doença. O objetivo deste estudo foi determinar a relação entre a dosagem de antígenos de Taenia mo LCR com as imagens obtidas através da RM, em pacientes com o diagnóstico definido de NC segundo os critérios diagnósticos atuais. Sessenta e três pacientes foram submetidos a exame detalhado do LCR, além de pesquisa de antígeno de Taenia através de teste de ELISA, utilizando anticorpos de soro de coelhos imunizados com líquido vesicular de Taenia crassiceps. Uma amostra de sangue foi colhida simultaneamente à coleta do LCR, e um exame de RM encefálica foi realizado em todos os pacientes. Observamos relação significativa entre a detecção de antígenos de Taenia e o número total de lesões e do número de cistos íntegros detectados pela RM. Quando comparados dois ou mais cistos em degeneração com apenas um cisto, observamos detecção significativamente mais alta no primeiro grupo. Encontramos também detecção de antígenos significativamente mais alta quando as lesões se localizavam na profundidade dos hemisférios cererbrais, mas não na presença de cistos calcificados. Os resultados demonstram que a detecção de antígenos de Taenia se mostra congruente com os achados de neuroimagem. Algumas outras variáveis estudadas no LCR, como número de células, teor de globulinas gama e teste de ELISA, também se mostraram concordantes, demonstrando que a resposta inflamatória na NC mobiliza tanto a imunidade celular quanto a imunidade humoral. / Neurocysticercosis (NC) is the most common parasitic infection of the nervous system, remaining a serious public health in our country. NC diagnosis is supported by clinical and epidemiological data, specific serological reactions in the blood and CSF, and neuroimaging findings. Detection of anti-Taenia antigens using ELISA techniques is a recent methodology that provides information about clinical activity of the disease. The objective of the study was to determine relationship between Taenia antigen detection in the CSF and MRI in patients with definite diagnosis of NC according to current diagnostic criteria. Sixty-three patients were submitted to a thorough CSF examination and Taenia antigen research. Antigens were detected in CSF samples by ELISA assay obtained from rabbit sera antibodies immunized with Taenia crassiceps cysticerci vesicular fluid. A blood sample was simultaneously collected and a MRI was performed in every patient. We observed a significant relationship between Taenia antigen detection and the total number of lesions and intact cysts detected by MRI. When comparing two or more degenerating cysts with only one we observed a significant higher antigen detection in the first group. We also found a significant higher antigen detection when cysts were deeply located in the cerebral hemispheres, but not in the presence of calcified cysts. Results demonstrate that Taenia antigen detection is congruent with neuroimaging findings. Some CSF characteristics, like number of cells, gamma globulin concentration and ELISA assay were also concordant with Taenia antigen detection, indicating that inflammatory reaction in NC comprise cellular and humoral immunological factors.

A meningite bacteriana no período neonatal é uma doença grave, associada à mortalidade elevada e seqüelas em cerca de 12 a 29% dos sobreviventes. Nos recém-nascidos com peso ao nascimento < 2500 g, o risco de adquirir meningite é três vezes superior àqueles com peso >= 2500 g e, entre neonatos de muito baixo peso (< 1500 g), o risco é 17 vezes maior. Objetivo: Geral: descrever o quadro clínico e as complicações da meningite bacteriana em dois grupos de recém-nascidos, considerados de acordo com o peso de nascimento (= 2500 g). Específico: descrever e comparar os agentes etiológicos, a freqüência de sinais e sintomas neurológicos e de complicações, a mortalidade e a duração do tratamento nos dois grupos. Métodos: Estudo observacional de 87 recém-nascidos com meningite bacteriana, admitidos na Unidade de Cuidados Intensivos Neonatais do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 11 anos (janeiro de 1994 a dezembro de 2004). Os dados foram obtidos através da análise de prontuários. Na análise estatística foram utilizados o teste exato de Fisher e teste não paramétrico de Mann Whitney. Resultados: Foram identificadas bactérias no líquor em 39% dos pacientes, sendo 50% bactérias Gram-positivas e 50% Gram-negativas. A maioria dos neonatos apresentou sinais e sintomas inespecíficos: febre (63,2%), irritabilidade (31%), letargia (26,4%). Os achados neurológicos ocorreram em 35,3% dos casos. As complicações ocorreram em 48,2% dos neonatos, principalmente convulsões (23%), hemorragia intracraniana (14,9%) e hidrocefalia (13,8%) com mortalidade de 11,5 %. Na comparação entre evolução clínica e peso de nascimento observou-se associação entre peso >= 2500 g e convulsão (p=0,047), peso >= 2500 g e fontanela abaulada (p=0,019), bactéria no LCR e complicações (p=0,008) e bactéria no LCR e óbitos (p=0,043). Conclusões: Os agentes etiológicos mais freqüentemente identificados no LCR foram as enterobactérias (41%), seguidas de Streptococcus B (17,5%), Streptococcus não B (17,5%), Staphylococcus aureus (11,7%), Neisseria meningitidis (8,8%) e Enterococcus faecalis (3,0%), não havendo diferença entre tipo de bactérias e peso de nascimento. Os sinais e sintomas predominantes foram inespecíficos, com achados neurológicos em 35% dos casos. A freqüência maior de sintomas neurológicos nos recém-nascidos com peso >= 2500 g, sugere maior grau de maturidade do sistema nervoso central nestas crianças. Embora a mortalidade tenha sido inferior à observada em estudos anteriores no mesmo Serviço, a freqüência de complicações foi alta, independentemente do peso de nascimento. A presença de bactéria no LCR associou-se à maior freqüência de convulsões e mortalidade. A necessidade de manutenção do tratamento por tempo mais prolongado nos recém-nascidos de baixo peso sugere maior gravidade da doença neste grupo de neonatos. / Bacterial meningitis in the neonatal period is a severe disease, associated to elevated mortality and sequelae in around 12 to 29% of the survivors. Newborns whose birth weight is < 2,500g have a 3-fold increase in the risk of acquiring meningitis when compared to those whose weight is >= 2,500; among those with very low birth weight (< 1,500g), the risk increases 17-fold. Objectives: General: to describe the clinical picture and the complications of bacterial meningitis in two groups of newborns, considered according to birth weight (< 2,500g or >= 2,500g). Specific: to describe and compare the etiological agents, the frequency of neurological signs and symptoms and complications, mortality rate and duration of treatment in both groups. Methods: Observational study of 87 newborns with bacterial meningitis, admitted at the Neonatal Intensive Care Unit (NICU) of Instituto da Criança of Hospital das Clínicas of the University of São Paulo School of Medicine, during an 11-year period (January 1994 to December 2004). The data were obtained through the analysis of hospital files. Statistical analysis was carried out with Fisher\'s exact test and the non-parametric Mann Whitney test. Results: Bacteria were identified in the cerebrospinal fluid (CSF) of 39% of the patients, with 50% of them being Gram-positive and 50%, Gram-negative. Most neonates presented unspecific signs and symptoms: fever (63.2%), irritability (31%), and lethargy (26.4%). The neurological findings occurred in 35.3% of the cases. Complications occurred in 48.2% of the neonates, and were mainly seizures (23%), intracranial hemorrhage (14.9%) and hydrocephalus (13.8%) with a mortality rate of 11.5%. At the comparison between clinical evolution and birth weight, associations between weight >= 2,500g and seizures (p=0.047), weight >= 2,500g and concave fontanel (p=0.019), bacteria in the CSF and complications (p=0.008) and bacteria in the CSF and death (p=0.043) were observed. Conclusions: The etiological agents most often identified in the CSF were enterobacteria (41%), followed by B Streptococcus (17.5%), non-B Streptococcus (17.5%), Staphylococcus aureus (11.7%), Neisseria meningitidis (8.8%) and Enterococcus faecalis(3.0%), with no statistical difference between the type of bacteria and birth weight. The predominant signs and symptoms were unspecific, with neurological findings in 35% of the cases. The higher frequency of neurological signs and symptoms in newborns with birth weight >= 2,500g suggest a higher degree of central nervous system maturity in these infants. Although the mortality was lower than that observed in previous studies at the same Service, the frequency of complications was high, regardless of birth weight. The presence of bacteria in the CSF was associated to a higher frequency of seizures and mortality. The need for prolonged treatment in newborns with low birth weight suggests higher disease severity in this group of neonates.

A meningite bacteriana no período neonatal é uma doença grave, associada à mortalidade elevada e seqüelas em cerca de 12 a 29% dos sobreviventes. Nos recém-nascidos com peso ao nascimento < 2500 g, o risco de adquirir meningite é três vezes superior àqueles com peso >= 2500 g e, entre neonatos de muito baixo peso (< 1500 g), o risco é 17 vezes maior. Objetivo: Geral: descrever o quadro clínico e as complicações da meningite bacteriana em dois grupos de recém-nascidos, considerados de acordo com o peso de nascimento (= 2500 g). Específico: descrever e comparar os agentes etiológicos, a freqüência de sinais e sintomas neurológicos e de complicações, a mortalidade e a duração do tratamento nos dois grupos. Métodos: Estudo observacional de 87 recém-nascidos com meningite bacteriana, admitidos na Unidade de Cuidados Intensivos Neonatais do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 11 anos (janeiro de 1994 a dezembro de 2004). Os dados foram obtidos através da análise de prontuários. Na análise estatística foram utilizados o teste exato de Fisher e teste não paramétrico de Mann Whitney. Resultados: Foram identificadas bactérias no líquor em 39% dos pacientes, sendo 50% bactérias Gram-positivas e 50% Gram-negativas. A maioria dos neonatos apresentou sinais e sintomas inespecíficos: febre (63,2%), irritabilidade (31%), letargia (26,4%). Os achados neurológicos ocorreram em 35,3% dos casos. As complicações ocorreram em 48,2% dos neonatos, principalmente convulsões (23%), hemorragia intracraniana (14,9%) e hidrocefalia (13,8%) com mortalidade de 11,5 %. Na comparação entre evolução clínica e peso de nascimento observou-se associação entre peso >= 2500 g e convulsão (p=0,047), peso >= 2500 g e fontanela abaulada (p=0,019), bactéria no LCR e complicações (p=0,008) e bactéria no LCR e óbitos (p=0,043). Conclusões: Os agentes etiológicos mais freqüentemente identificados no LCR foram as enterobactérias (41%), seguidas de Streptococcus B (17,5%), Streptococcus não B (17,5%), Staphylococcus aureus (11,7%), Neisseria meningitidis (8,8%) e Enterococcus faecalis (3,0%), não havendo diferença entre tipo de bactérias e peso de nascimento. Os sinais e sintomas predominantes foram inespecíficos, com achados neurológicos em 35% dos casos. A freqüência maior de sintomas neurológicos nos recém-nascidos com peso >= 2500 g, sugere maior grau de maturidade do sistema nervoso central nestas crianças. Embora a mortalidade tenha sido inferior à observada em estudos anteriores no mesmo Serviço, a freqüência de complicações foi alta, independentemente do peso de nascimento. A presença de bactéria no LCR associou-se à maior freqüência de convulsões e mortalidade. A necessidade de manutenção do tratamento por tempo mais prolongado nos recém-nascidos de baixo peso sugere maior gravidade da doença neste grupo de neonatos. / Bacterial meningitis in the neonatal period is a severe disease, associated to elevated mortality and sequelae in around 12 to 29% of the survivors. Newborns whose birth weight is < 2,500g have a 3-fold increase in the risk of acquiring meningitis when compared to those whose weight is >= 2,500; among those with very low birth weight (< 1,500g), the risk increases 17-fold. Objectives: General: to describe the clinical picture and the complications of bacterial meningitis in two groups of newborns, considered according to birth weight (< 2,500g or >= 2,500g). Specific: to describe and compare the etiological agents, the frequency of neurological signs and symptoms and complications, mortality rate and duration of treatment in both groups. Methods: Observational study of 87 newborns with bacterial meningitis, admitted at the Neonatal Intensive Care Unit (NICU) of Instituto da Criança of Hospital das Clínicas of the University of São Paulo School of Medicine, during an 11-year period (January 1994 to December 2004). The data were obtained through the analysis of hospital files. Statistical analysis was carried out with Fisher\'s exact test and the non-parametric Mann Whitney test. Results: Bacteria were identified in the cerebrospinal fluid (CSF) of 39% of the patients, with 50% of them being Gram-positive and 50%, Gram-negative. Most neonates presented unspecific signs and symptoms: fever (63.2%), irritability (31%), and lethargy (26.4%). The neurological findings occurred in 35.3% of the cases. Complications occurred in 48.2% of the neonates, and were mainly seizures (23%), intracranial hemorrhage (14.9%) and hydrocephalus (13.8%) with a mortality rate of 11.5%. At the comparison between clinical evolution and birth weight, associations between weight >= 2,500g and seizures (p=0.047), weight >= 2,500g and concave fontanel (p=0.019), bacteria in the CSF and complications (p=0.008) and bacteria in the CSF and death (p=0.043) were observed. Conclusions: The etiological agents most often identified in the CSF were enterobacteria (41%), followed by B Streptococcus (17.5%), non-B Streptococcus (17.5%), Staphylococcus aureus (11.7%), Neisseria meningitidis (8.8%) and Enterococcus faecalis(3.0%), with no statistical difference between the type of bacteria and birth weight. The predominant signs and symptoms were unspecific, with neurological findings in 35% of the cases. The higher frequency of neurological signs and symptoms in newborns with birth weight >= 2,500g suggest a higher degree of central nervous system maturity in these infants. Although the mortality was lower than that observed in previous studies at the same Service, the frequency of complications was high, regardless of birth weight. The presence of bacteria in the CSF was associated to a higher frequency of seizures and mortality. The need for prolonged treatment in newborns with low birth weight suggests higher disease severity in this group of neonates.

Eine der häufigsten viralen Infektionskrankheiten im Kindesalter ist gegenwärtig die Parotitis epidemica. Mit dem Auftreten einer abakteriellen Meningitis bei Kindern als Folge einer Mumpsvirusinfektion ist in über 80% der Fälle zu rechnen. 1. In serologisch bestätigten Mumpsfällen wurden Liquorproben von Kindern mit einer Meningitis immunfluoreszenzoptisch untersucht. In den lympho-monozytären Liquorzellen konnte das Mumpsantigen in 64% der Fälle nachgewiesen werden. 2. Der immunfluoreszenzoptisch Nachweis des Mumpsantigens in Liquorzellen stellt eine Erweiterung der diagnostischen Möglichkeiten bei serösen Meningitiden des Kindes unklarer Äthiologie dar. 3. Während der Prüfung von Mumpsviren reagieren intracerebral infizierte Affen mit einer statistisch gesicherten Erhöhung der Liquorzellzahl. Bei Affen, die mit einer neuropathogenen Variante infiziert waren, sind die Liquorzellzahlen auch 28 Tage p.i. signifikant höher im Vergleich zu mit Impfstoff infizierten Tieren. Der Nachweis des Mumpsantigens in den Liquorzellen beweist die Spezifität der experimentellen Mumpsmeningitis bei Affen. Das virale Antigen wird nur innerhalb der ersten Versuchswoche in den Liquorzellen detektiert, nach 3 – 4wöchiger Versuchsdauer ist das Mumpsvirus im Liquor der Affen nicht mehr nachweisbar. Diese Befunde sind mit den Befunden bei natürlichen Mumpsmeningitiden der Kinder vergleichbar. 4. Minischweine und Katzen reagieren auf intracerebral appliziertes Mumpsvirus mit charakteristischen liquorzytologischen Veränderungen, die mit den Befunden beim Affen korrelieren. Sie reagieren auf intracerebral inokuliertes Mumpsvirus bereits in der ersten Woche mit einer deutlichen Liquorpleozytose. Die Höhe der Zellzahl im Liquor ist bei Mumpswildviren (α = 0,05) bedeutend größer als bei den Impfviren. Die Zellzahlerhöhung ist nach 8 Wochen nicht auf die Normalwerte zurückgegangen. 5. Der immunfluoreszenzoptische Nachweis des Mumpsantigens in den Liquorzellen der Minischweine und Katzen ist zeitlich begrenzt. Es ergaben sich Unterschiede zwischen Mumpsviren vom Wild- und Impftyp. Der Nachweis des viralen Antigens in den Liquorzellen war 4 Wochen p.i. nicht mehr möglich. 6. Das Differentialzellbild des Liquors ist bei allen Tiermodellen durch lympho-monozytäre Zellen gekennzeichnet, wobei monozytäre Zellformen zu jedem Zeitpunkt der Infektion überwiegen. 7. Vor der Anwendung von Lebendimpfstoffen beim Menschen ist eine tierexperimentelle Sicherheitsprüfung notwendig. Die Einbeziehung der Liquordiagnostik (Verlauf der Pleozytose und der fluoreszenzoptische Antigennachweis in den Liquorzellen) ist eine wesentliche Ergänzung zur Charakterisierung der neurotropen Eigenschaften des viralen Mumpsantigens. / One of the most common viral infectious diseases in childhood is currently parotitis epidemica. The occurrence of abacterial meningitis in children as a result of mumps virus infection can be expected in more than 80% of cases. 1. In serologically confirmed mumps cases, cerebrospinal fluid samples from children with meningitis were examined by immunofluorescence. Mumps antigen was detected in the lympho-monocytic cerebrospinal fluid (CSF) cells in 64% of cases. 2. Immunofluorescence detection of mumps antigen in CSF cells represents an extension of diagnostic possibilities in serous meningitis of the child of unclear etiology. 3. During mumps virus testing, intracerebrally infected monkeys respond with a statistically confirmed increase in CSF cell count. In monkeys infected with a neuropathogenic variant, CSF cell counts are significantly higher even 28 days p.i. compared with vaccine-infected animals. Detection of mumps antigen in CSF cells demonstrates the specificity of experimental mumps meningitis in monkeys. The viral antigen is detected in the CSF cells only within the first week of the experiment; after 3 - 4 weeks of the experiment, the mumps virus is no longer detectable in the CSF of the monkeys. These findings are comparable to the findings in natural mumps meningitis of children. 4. Minipigs and cats respond to intracerebrally applied mumps virus with characteristic liquor cytologic changes that correlate with the findings in monkeys. They respond to intracerebrally inoculated mumps virus with marked CSF pleocytosis as early as the first week. The level of cell number in CSF is significantly greater in wild mumps virus (α = 0.05) than in vaccine virus. The cell count increase did not return to normal values after 8 weeks. 5. Immunofluorescence detection of mumps antigen in CSF cells of minipigs and cats is temporal. Differences were found between wild-type and vaccine-type mumps viruses. Detection of viral antigen in CSF cells was no longer possible 4 weeks p.i.. 6. The differential cell pattern of CSF is characterized by lympho-monocytic cells in all animal models, with monocytic cell forms predominating at each time point of infection. 7. Animal safety testing is required prior the use of live vaccines in humans. The inclusion of CSF diagnostics (course of pleocytosis and fluorescence antigen detection in CSF cells) is an essential addition to characterize the neurotropic properties of the viral mumps antigen.

BACKGROUND:Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury.FINDINGS:Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes.CONCLUSIONS:This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.

O hormônio melatonina é produzido pela glândula pineal de mamíferos de forma circadiana e sua secreção é mais elevada durante a noite. Melatonina é liberada no sistema ventricular cerebral através do recesso pineal do 3º ventrículo. Sabe-se que a concentração de melatonina é maior nos ventrículos cerebrais que no plasma e no líquido cerebroespinhal lombar. Para avaliar a dinâmica da melatonina liquórica no rato Wistar, coletamos, através de microdiálise, amostras do líquor do terceiro ventrículo cerebral de animais jovens. Para avaliar a variação ontogenética em sua produção e liberação compararam-se as concentrações de melatonina liquórica em animais jovens e idosos. Observou-se também o perfil da melatonina liquórica em animais pinealectomizados. Esses procedimentos darão base para uma análise sistemática da dinâmica da melatonina no líquido cerebroespinal ventricular. / The hormone melatonin is produced by the mammalian pineal gland in a circadian way and its secretion is higher at night. Melatonin is released to the cerebral ventricular system through the pineal recess of the III ventricle. We know that the concentration of melatonin is higher in the cerebral ventricles than in plasma and lumbar cerebrospinal fluid. To evaluate the dynamic of melatonin in the cerebrospinal fluid (CSF) in Wistar rats, we collected, using microdialisys, samples of cerebrospinal fluid in the III ventricle of young animals. To estimate the ontogenetic decrease in melatonin production and release we compared the concentrations of CSF melatonin in young and aged animals. The concentration of CSF melatonin was also evaluated in pinealectomized rats. These procedures will elucidate the dynamic of ventricular CSF melatonin.