Die Azidose gehört zu den stärksten dilatatorischen Stimuli zerebraler Arterien. Obwohl schon 1890 von Roy und Sherrington beschrieben, sind die Faktoren, die die Vasodilatation zerebraler Arterien auf Azidose vermitteln, bis heute nicht bekannt. Untersuchungen über die Rolle des schnell flüchtigen Bioradikals Stickstoffmonoxid (NO) haben gezeigt, daß NO bei der azidotischen Vasodilatation zerebraler Arterien als Modulator agiert. Darüber hinaus nimmt NO in der neurovaskulären Kopplung, d.h. bei der Vermittlung der regionalen Blutflußantwort nach neuronaler Stimulation, eine permissive Funktion ein. Die Vasodilatation auf Azidose wurde in der vorliegenden Arbeit als Modellstimulus zur Untersuchung der NO-abhängigen Dilatation zerebraler Arterien verwendet. Dabei wurde die Rolle der Kaliumkanäle und die Funktion des cGMP an der Vasodilatation auf Azidose mittels spezifischer Inhibitoren untersucht. Die Experimente erfolgten an der isolierten und perfundierten A. cerebri media der Ratte. Bei der Untersuchung der Signaltransduktion von NO auf Ebene des cGMP wurde eine ausgeprägte Abhängigkeit der azidotischen Vasodilatation von cGMP beobachtet. Durch Restitution des basalen cGMP-Spiegels nach vorheriger Inhibition der löslichen Guanylatzyklase wurde gezeigt, daß NO über cGMP bei der Vermittlung dieser Reaktion als Modulator wirkt. Unter Blockade der einzelnen Kaliumkanalfamilien konnte eine Beteiligung der KCa an der Vasodilatation auf Azidose sowie am Gefäßtonus unter Ruhebedingungen beobachtet werden. Für eine Beteiligung der KATP, der KV und der Kir an diesen Reaktionen wurden dagegen keine Hinweise gefunden. Ebenso sprechen die Untersuchungen unter Blockade der Na+/K+-ATPase gegen eine Beteiligung dieses Enzyms an der Azidosereaktivität zerebraler Arterien. Um ein mögliches Zusammenwirken der Kaliumkanäle zu erfassen, wurde die Vasodilatation auf Azidose unter Blockade von jeweils zwei Kaliumkanaltypen untersucht. Unter Hemmung der KCa und der KATP, sowie unter Hemmung der BKCa und der KATP wurde keine Vasodilatation mehr auf Azidose beobachtet. Die Ergebnisse sprechen dafür, daß die Vasodilatation der A. cerebri media auf Azidose durch BKCa und KATP in redundanter Weise vermittelt wird. Dabei scheinen KCa die Funktion der KATP vollständig substituieren zu können. Die Resultate dieser Arbeit bilden den Ausgangspunkt für derzeit laufenden Untersuchungen über die funktionelle Modulation der KATP und der BKCa durch das NO/cGMP-System. Weiterhin bilden die vorliegenden Untersuchungen eine wichtige Grundlage zur Überprüfung der zentralen Rolle der KCa und der KATP auf weitere, durch das NO/cGMP-System modulierten Stimuli, wie z.B. der funktionellen Stimulation. Die in dieser Arbeit vorgestellten Experimente wurden mit Mitteln der Deutschen Forschungsgemeinschaft (SFB 507), der Hermann und Lilly Schilling Stiftung, sowie der Humboldt Universität zu Berlin gefördert. / Acidosis is one of the most potent vasodilators in the cerebral circulation. Although first described 1890 by Roy and Sherrington the mechanisms of vasodilation to acidosis are still unknown. Experimental data show, that nitric oxide (NO) is a modulator but not a mediator of cerebral arterial pH reactivity. NO also acts as a modulator of neurovascular coupling in the rat somatosensory cortex. We used the experimental in vitro model of the isolated and perfused middle cerebral artery (MCA) to elucidate the general mechanisms of NO-modulated dilations. The present study was performed to clarify the role of cGMP and potassium channels for mediation of acidosis-induced dilation of cerebral arteries. The results indicate, that vasodilation to acidosis is mediated by cGMP. Restoring the basal cGMP-level we could demonstrate a permissive role of cGMP in the vasodilation to acidosis. We could also show that KCa are active under resting conditions and are able to contribute to the relaxation of the MCA to acidosis. Other potassium channels like KATP, Kir, KV and the Na+/K+ATPase appeared not to be involved in the process of dilation to acidosis. After administration of a selective inhibitor of KATP in addition to an inhibitor of KCa the relaxation to acidosis was completely abolished. Simultaneous application of selective inhibitors of KATP and BKCa also prevented from vasodilation to acidosis. These results indicate, that relaxation to acidosis is mediated by activation of KATP and BKCa. This potassium channels seem to have a redundant activity, in such a way that KCa could substitute for KATP. The present findings are a starting point for further studies concerning the modulation of KATP and BKCa by the NO/cGMP-System. This studies are a basis for coming experiments to determine the role of KATP and BKCa in the neurovascular coupling.

Sabe-se que um bom fluxo sanguíneo colateral (FSC) leptomeníngeo está associado a melhor desfecho funcional em paciente com oclusão vascular da circulação anterior. Entretanto, poucos estudos avaliaram os preditores de FSC e seu impacto prognósticos em países em desenvolvimento. O objetivo deste trabalho é avaliar os preditores e o impacto prognóstico do FSC leptomeníngeo nas oclusões do primeiro segmento (M1) da Artéria Cerebral Média (ACM). Métodos: Foi avaliado de maneira retrospectiva, uma coorte prospectiva de pacientes com acidente vascular cerebral (AVC), admitidos em um centro terciário acadêmico de referência para o tratamento de AVC entre janeiro de 2014 e junho de 2017. Foram incluídos pacientes que apresentavam oclusão do segmento M1 da ACM e realizaram angiotomografia de crânio (AngioTC) até 12 horas após o ictus. O FSC foi analisado utilizando uma escala previamente validada na literatura, o rLMC score. Foi avaliado a relação do rLMC score com variáveis clínicas e com desfecho. Na análise univariada foi utilizado o teste de Fisher para variáveis categóricas e t de Student para variáveis quantitativas, também foi utilizado o teste de Spearman para correlação de variáveis contínuas. Características associadas com rLMC score e com desfecho funcional foram incluídas da regressão linear (rLMC não categorizado) e regressão logística binária (rLMC categorizado). Foi utilizado um valor de significância estatística convencional (p=0,05) Resultados: Dos 1559 pacientes com AVC isquêmico admitidos, foram analisados 121 pacientes que preencheram critérios de inclusão/exclusão do estudo. A idade média foi de 67.1±15 anos, NIHSS 13 [IQR 11-22]. Na regressão linear, menor idade (? = -0.2; p=0.005), Doença de14 Chagas (? = 0,22; p=0,008), Tabagismo (? = 0,22; p=0,009), menor NIHSS (? = - 0,25; p=0,002) e história de doença coronariana (? = 0,23; p=0,005) foram associados com melhor rLMC score. Menor idade (? = 0,29; p<0,001), menor NIHSS (? = 0,36; p<0,001) e rLMC>= 17 (? = -0,16; p=0,04) foram associados com melhor desfecho clínico. Conclusão: Pacientes com bom FSC leptomeníngeo apresentam menor NIHSS, menor idade, maior frequência de doença de Chagas, história de tabagismo e doença coronariana prévia. Um bom FSC leptomeníngeo está associado a melhor desfecho funcional entre paciente com AVC isquêmico por oclusão de artérias proximais da circulação anterior no Brasil. / A Good leptomeningeal collateral flow has been associated with better outcomes in patients with proximal occlusions of the anterior circulation. Nevertheless, only few studies have assessed the predictors of good leptomeningeal collateral flow and its impact on clinical outcome in developing countries. We aim to evaluate predictors and prognostic impact of leptomeningeal collateral flow among patients with proximal middle cerebral artery (MCA) occlusion. Method: We retrospectively analyzed a prospective stroke registry of AIS patients admitted to a tertiary Stroke Center in Brazil, with MCA-M1 occlusion within twelve hours of symptoms onset, admitted from January 2014-June 2017. Leptomeningeal score was evaluated using a previously validated Regional Leptomeningeal (rLMC) score. We evaluated association between rLMC score with clinical variables and outcomes. Univariate analysis was performed using Fisher exact test for categorical variables and t-Student for continuous variables. Spearman\'s correlation analysis was performed to find the relationship between continuous variables and rLMC. Variables were included in linear regression model (non categorized rLMC) or binary logistic regression model (categorized rLMC). Conventional levels of statistical significance were used (p=0.05). Results: From 1559 AIS patients, 121 were analyzed. Demographics: age 67.1±15 years, NIHSS 13 [IQR 11-22]. In linear regression, lower age (? = -0.2; p=0.021), Chagas Disease (? = 0.22; p=0.008), smoking (? = 0.22; p=0.009), lower NIHSS (? = -0.25; p=0.002) and history of coronary artery disease (? = 0.23; p=0,005) were associated with better rLMC score. Lower age (? = 0.29; p<0.001), lower NIHSS (? = 0.36; p<0.001) and rLMC>= 17 (? = -0.16; p=0.04) were associated with better functional outcomes. Conclusion: Patients with good leptomeningeal collateral flow had lower age, lower NIHSS, Chagas disease and history of smoking. Good leptomeningeal collaterals on CT angiography are associated to good outcome among AIS patients with proximal arterial occlusion of the anterior circulation in Brazil.

Li Huan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (p. 285-306). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

Idiopathic Normal Pressure Hydrocephalus (INPH) is a condition affecting gait, cognition and continence. Radiological examination reveals enlarged ventricles of the brain. A shunt that drains CSF from the ventricles to the abdomen often improves the symptoms. Much research on INPH has been focused on identifying tests that predict the outcome after shunt surgery. As part of this quest, there are attempts to find measurement methods of intracranial parameters that are valid, reliable, tolerable and safe for patients. Today's technologies for intracranial pressure (ICP) measurement are invasive, often requiring a burr-hole in the skull. Recently, a method for non-invasive ICP measurements was suggested: the Pulsatile Index (PI) calculated from transcranial Doppler data assessed from the middle cerebral artery. In this thesis the relation between PI and ICP was explored in INPH patients during controlled ICP regulation by lumbar infusion. The confidence interval for predicted ICP, based on measured PI was too large for the method to be of clinical utility. In the quest for better predictive tests for shunt success in INPH, recent studies have shown promising results with criteria based on cardiac related ICP wave amplitudes. The brain ventricular system, and the fluid surrounding the spinal cord are in contact. In this thesis it was shown that ICP waves could be measured via lumbar subarachnoid space, with a slight underestimation. One of the cardinal symptoms of hydrocephalus is cognitive impairment. Neuropsychological studies have demonstrated cognitive tests that are impaired and improve after shunt surgery in INPH patients. However, there is currently no standardized test battery and different studies use different tests. In response, in this thesis a fully automated computerized neuropsychological test battery was developed. The validity, reliability, responsiveness to improvement after shunt surgery and feasibility for testing INPH patients was demonstrated. It was also demonstrated that INPH patients were impaired in all subtests, compared to healthy elderly.

No description available.

No description available.

Vitronectin (VTN) is a glycoprotein enriched in the blood and activates integrin receptors. VTN blood levels increase only in female mice 24 h after an ischemic stroke and exacerbate brain injury through IL-6-driven inflammation, but the VTN induction mechanism is unknown. Here, a 30 min middle cerebral artery occlusion (MCAO) in female mice induced VTN protein in the liver (normally the main source) in concert with plasma VTN. Male mice were excluded as VTN is not induced after stroke. MCAO also increased plasma VTN levels after de novo expression of VTN in the liver of VTN female mice, using a hepatocyte-specific (SERPINA1) promoter. MCAO did not affect SERPINA1 or VTN mRNA in the liver, brain, or several peripheral organs, or platelet VTN, compared to sham mice. Thus, hepatocytes are the source of stroke-induced increases in plasma VTN, which is independent of transcription. The cholinergic innervation by the parasympathetic vagus nerve is a potential source of brain-liver signaling after stroke. Right-sided vagotomy at the cervical level led to increased plasma VTN levels, suggesting that VTN release is inhibited by vagal tone. Co-culture of hepatocytes with cholinergic neurons or treatment with acetylcholine, but not noradrenaline (sympathetic transmitter), suppressed VTN expression. Hepatocytes have muscarinic receptors and the M1/M3 agonist bethanechol decreased VTN mRNA and protein release in vitro via M1 receptors. Finally, systemic bethanechol treatment blocked stroke-induced plasma VTN. Thus, VTN translation and release are inhibited by muscarinic signaling from the vagus nerve and presents a novel target for lessening detrimental VTN expression.

Dissertation (Ph.D.)--University of South Florida, 2009. / Title from PDF of title page. Document formatted into pages; contains 164 pages. Includes vita. Includes bibliographical references.

Objetivo: Avaliar a relação das alterações de fluxo na artéria cerebral média (ACM) com a ocorrência de acidemia no nascimento, em gestações com insuficiência placentária. Métodos: estudo transversal prospectivo com 91 gestações com diagnóstico de insuficiência placentária pelo Doppler de artéria umbilical (AU) alterado (índice de pulsatilidade [IP] > p95). Os critérios de inclusão foram: gestações únicas com idade gestacional (IG) superior a 26 semanas completas, membranas ovulares íntegras, ausência de anomalias cromossômicas ou congênitas. Os parâmetros da dopplervelocimetria analisados foram: IP da AU, IP da ACM, pico de velocidade sistólica (PVS) da ACM, relação cerebroplacentária (RCP) e índice de pulsatilidade para veias (IPV) do ducto venoso (DV). Foi analisada a última avaliação fetal realizada imediatamente antes do parto ou anterior à corticoterapia. Todos os parâmetros foram analisados por meio do escore zeta ou múltiplos da mediana (MoM), baseados nas médias, desvio-padrão e valores de referência para cada IG. Imediatamente após o parto, uma amostra de sangue da artéria umbilical foi obtida para a medida do pH, e os casos classificados de acordo com a presença (pH < 7,20) ou ausência de acidemia no nascimento. Resultados: Quarenta e sete (51,6%) recémnascidos apresentaram acidemia no nascimento. Os fetos que evoluíram com acidemia apresentaram valor de escore zeta do IP da AU significativamente maior (mediana 2,1 vs 1,7; p=0,014), assim como maior proporção de casos com diástole zero ou reversa (51,0% vs 31,8%; p=0,006). Quanto à ACM, o escore zeta mostrou-se significativamente menor nos casos com pH < 7,20 (mediana -2,7 vs -2,1; p=0,042), porém, em relação ao PVS não foi possível estabelecer diferença significativa entre os grupos (p=0,051). A acidemia no nascimento se associou a menores valores de RCP (mediana 0,5 vs 0,7; p=0,006), porém não ao seu escore zeta (p=0,055). Em relação ao território venoso, maiores valores do escore zeta do IPV do DV associaram-se à acidemia (mediana 2,4 vs 0,6; p=0,015). Na análise de correlação entre os valores de pH no nascimento e os resultados da avaliação da dopplervelocimetria fetal, foi constatada correlação significativa entre o valor do pH no nascimento e o escore zeta do IP da AU (rho=-0,31; p=0,003), IP da ACM (rho=0,26; p=0,012), da RCP (rho 0,25; p=0,015) e IPV do DV (rho=-0,32; p=0,002), e PVS da ACM MoM (rho=-0,21; p=0,042). A regressão logística identificou o escore zeta do IP da AU e escore zeta IP da ACM como variáveis independentes para a predição de acidemia no nascimento, classificando corretamente 67,03% dos casos. Conclusão: em casos de insuficiência placentária, o IP da AU e da ACM são preditores independentes associados com a acidemia no nascimento. Este estudo reforça que o grau de insuficiência placentária e a capacidade de adaptação fetal estão diretamente relacionados com a acidemia no nascimento / Objectives: To evaluate the relationship between middle cerebral artery (MCA) parameters and acidemia at birth, in pregnancies complicated by placental insufficiency. Methods: The study was performed as a prospective cross-sectional analysis of Doppler measurements in 91 patients with the diagnosis of placental dysfunction by abnormal umbilical artery (UA) Doppler (pulsatility index [PI] > p95). Inclusion criteria were: singleton pregnancy, intact membranes, abscence of fetal congenital or chromosomal abnormalities. The Doppler parameters analyzed were: UA PI, MCA PI, MCA peak systolic velocity (PSV), cerebroplacental ratio (CPR) and pulsatilility index for veins (PIV) of ductus venosus (DV). It was analyzed the last assessment obtained right before birth or the antenatal steroids. Umbical artey blood samples were collected at birth, and acidemia was defined as pH below 7.20. Results: Forty seven (51.6%) newborns had acidemia at birth. Those who developed acidemia showed a UA PI z-score significantly higher (median 2.1 vs 1.7, p = 0.014), as well as a higher proportion of cases with absent or reverse end diastolic flow (51.0% vs 31.8%, p = 0.006). Regarding the MAC, the PI z-score was significantly lower in cases with pH < 7.20 (median -2.7 vs. -2.1, p = 0.042), but concerning PSV z-score, no significant relation between the groups could be established (p = 0.051).The acidemia at birth was associated with lower values of CPR (median 0.5 vs 0.7, p = 0.006), but not with its z-score (p = 0.055). In relation to the venous territory, greater values of DV PIV z-score were associated with acidemia (median 2.4 vs 0.6, p = 0.015).The correlation analysis between the pH values at birth and the Doppler measurements, a significant correlation was observed between the pH at birth and UA PI z-score (rho = -0.31, p = 0.003 ), MCA PI z-score (rho = 0.26, p = 0.012), CPR z-score (rho 0.25, p = 0.015), PIV DV zscore (rho = -0.32, p = 0.002), and PSV MCA MoM (rho = -0.21, p = 0.042). Logistic regression identified the UA PI z-score and the MCA PI z-score as independent predictors for acidemia at birth, correctly classifying 67.03% of cases. Conclusion: In pregnancies with placental insufficiency, the UA PI and the MCA PI are independent predictors associated with acidemia at birth. This study reinforces that the degree of placental insufficiency and the fetal adaptation capacity are directly related to acidemia at birth

Objetivo: Avaliar a relação das alterações de fluxo na artéria cerebral média (ACM) com a ocorrência de acidemia no nascimento, em gestações com insuficiência placentária. Métodos: estudo transversal prospectivo com 91 gestações com diagnóstico de insuficiência placentária pelo Doppler de artéria umbilical (AU) alterado (índice de pulsatilidade [IP] > p95). Os critérios de inclusão foram: gestações únicas com idade gestacional (IG) superior a 26 semanas completas, membranas ovulares íntegras, ausência de anomalias cromossômicas ou congênitas. Os parâmetros da dopplervelocimetria analisados foram: IP da AU, IP da ACM, pico de velocidade sistólica (PVS) da ACM, relação cerebroplacentária (RCP) e índice de pulsatilidade para veias (IPV) do ducto venoso (DV). Foi analisada a última avaliação fetal realizada imediatamente antes do parto ou anterior à corticoterapia. Todos os parâmetros foram analisados por meio do escore zeta ou múltiplos da mediana (MoM), baseados nas médias, desvio-padrão e valores de referência para cada IG. Imediatamente após o parto, uma amostra de sangue da artéria umbilical foi obtida para a medida do pH, e os casos classificados de acordo com a presença (pH < 7,20) ou ausência de acidemia no nascimento. Resultados: Quarenta e sete (51,6%) recémnascidos apresentaram acidemia no nascimento. Os fetos que evoluíram com acidemia apresentaram valor de escore zeta do IP da AU significativamente maior (mediana 2,1 vs 1,7; p=0,014), assim como maior proporção de casos com diástole zero ou reversa (51,0% vs 31,8%; p=0,006). Quanto à ACM, o escore zeta mostrou-se significativamente menor nos casos com pH < 7,20 (mediana -2,7 vs -2,1; p=0,042), porém, em relação ao PVS não foi possível estabelecer diferença significativa entre os grupos (p=0,051). A acidemia no nascimento se associou a menores valores de RCP (mediana 0,5 vs 0,7; p=0,006), porém não ao seu escore zeta (p=0,055). Em relação ao território venoso, maiores valores do escore zeta do IPV do DV associaram-se à acidemia (mediana 2,4 vs 0,6; p=0,015). Na análise de correlação entre os valores de pH no nascimento e os resultados da avaliação da dopplervelocimetria fetal, foi constatada correlação significativa entre o valor do pH no nascimento e o escore zeta do IP da AU (rho=-0,31; p=0,003), IP da ACM (rho=0,26; p=0,012), da RCP (rho 0,25; p=0,015) e IPV do DV (rho=-0,32; p=0,002), e PVS da ACM MoM (rho=-0,21; p=0,042). A regressão logística identificou o escore zeta do IP da AU e escore zeta IP da ACM como variáveis independentes para a predição de acidemia no nascimento, classificando corretamente 67,03% dos casos. Conclusão: em casos de insuficiência placentária, o IP da AU e da ACM são preditores independentes associados com a acidemia no nascimento. Este estudo reforça que o grau de insuficiência placentária e a capacidade de adaptação fetal estão diretamente relacionados com a acidemia no nascimento / Objectives: To evaluate the relationship between middle cerebral artery (MCA) parameters and acidemia at birth, in pregnancies complicated by placental insufficiency. Methods: The study was performed as a prospective cross-sectional analysis of Doppler measurements in 91 patients with the diagnosis of placental dysfunction by abnormal umbilical artery (UA) Doppler (pulsatility index [PI] > p95). Inclusion criteria were: singleton pregnancy, intact membranes, abscence of fetal congenital or chromosomal abnormalities. The Doppler parameters analyzed were: UA PI, MCA PI, MCA peak systolic velocity (PSV), cerebroplacental ratio (CPR) and pulsatilility index for veins (PIV) of ductus venosus (DV). It was analyzed the last assessment obtained right before birth or the antenatal steroids. Umbical artey blood samples were collected at birth, and acidemia was defined as pH below 7.20. Results: Forty seven (51.6%) newborns had acidemia at birth. Those who developed acidemia showed a UA PI z-score significantly higher (median 2.1 vs 1.7, p = 0.014), as well as a higher proportion of cases with absent or reverse end diastolic flow (51.0% vs 31.8%, p = 0.006). Regarding the MAC, the PI z-score was significantly lower in cases with pH < 7.20 (median -2.7 vs. -2.1, p = 0.042), but concerning PSV z-score, no significant relation between the groups could be established (p = 0.051).The acidemia at birth was associated with lower values of CPR (median 0.5 vs 0.7, p = 0.006), but not with its z-score (p = 0.055). In relation to the venous territory, greater values of DV PIV z-score were associated with acidemia (median 2.4 vs 0.6, p = 0.015).The correlation analysis between the pH values at birth and the Doppler measurements, a significant correlation was observed between the pH at birth and UA PI z-score (rho = -0.31, p = 0.003 ), MCA PI z-score (rho = 0.26, p = 0.012), CPR z-score (rho 0.25, p = 0.015), PIV DV zscore (rho = -0.32, p = 0.002), and PSV MCA MoM (rho = -0.21, p = 0.042). Logistic regression identified the UA PI z-score and the MCA PI z-score as independent predictors for acidemia at birth, correctly classifying 67.03% of cases. Conclusion: In pregnancies with placental insufficiency, the UA PI and the MCA PI are independent predictors associated with acidemia at birth. This study reinforces that the degree of placental insufficiency and the fetal adaptation capacity are directly related to acidemia at birth