Salvinorin A preserves cerebral pial artery autoregulation after forebrain ischemia via the PI3K/AKT/cGMP pathway

This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR) control group received DMSO (1 µL/kg) immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg) were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg) and LY294002 (10 µM), L-NAME (10 μM), or norbinaltorphimine (norBIN, 1 μM) after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF) were also measured. The phosphorylation of AKT (p-AKT) was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE) and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.

Plasma Total Homocysteine Level Is Associated with the Pulsatility Index of Cerebral Arteries in Lacunar Infarction

PURPOSE: The pulsatility index (PI), measured by transcranial Doppler (TCD), is a surrogate marker for distal vascular resistance in cerebral arteries, and elevated plasma total homocysteine (tHcyt) is regarded as a cause of ischemic stroke, including lacunar infarction. We investigated the relationship between the PI of cerebral arteries and plasma tHcyt in patients with lacunar infarction. MATERIALS AND METHODS: Plasma tHcyt level and TCD examination were performed in 94 patients with lacunar infarction. Mean flow velocity (MFV) and PI were assessed at the ipsilateral middle cerebral artery (MCA) and contralateral MCA, relative to the infarction, and the basilar artery (BA). Multivariate regression analysis was conducted between log-transformed tHcyt levels (logHcyt) and the PI of individual arteries. RESULTS: There was a significant correlation between logHcyt and the PI in all tested arteries (ipsilateral MCA: r=0.21, p=0.03; contralateral MCA: r=0.21, p=0.04; BA: r=0.35, p=0.01). In multivariate regression analysis, this significance remained unchanged after adjusting for vascular risk factors, creatinine, hematocrit and platelet count (ipsilateral MCA: beta=0.26, p=0.01; contralateral MCA: beta=0.21, p=0.04; BA: beta=0.39, p=0.001). There was no significant association between logHcyt and MFV of individual arteries. CONCLUSION: A significant association between plasma tHcyt and the PI of cerebral arteries indicates that homocysteine plays a role in the increase of distal arterial resistance in lacunar infarction.

Evaluación de la función cardiovascular en fetos con restricción de crecimiento / Cardiac function in fetus with growth restriction

Objective: To evaluate longitudinal changes in the cardiac function parameters in relation to the hemodynamic worsening in growth restricted (IUGR) fetuses. Methods: The cardiac function was serially studied in a cohort of 46 IUGR fetuses below 32 weeks of gestation by 2-D and Doppler ultrasound parameters. IUGR was defined as an estimated fetal weight below the 10th percentile with a Doppler pulsatility index (PI) in the umbilical artery (UA) above 2 standard deviations of the mean. Longitudinal changes, perinatal deaths and survivors were evaluated. Results: All cardiac parameters were significantly different in IUGR fetuses. Aortic isthmus blood flow index (IFI) and Modified myocardial performance index (Mod-MPI) showed the clearest longitudinal changes and temporal deterioration. Conclusions: IFI and Mod-MPI showed consistent longitudinal changes in IUGR fetuses. These 2 markers could be added to the DV to evaluate the fetal deterioration and indicate the optimal time of delivery.

Objetivo: Evaluar cambios longitudinales de los parámetros de función cardíaca en relación al agravamiento hemodinámico en fetos con restricción del crecimiento intrauterino (RCIU). Métodos: La función cardíaca fue estudiada en una cohorte de 46 fetos RCIU con menos de 32 semanas de gestación con parámetros 2-D y ultrasonografía Doppler. Se definió RCIU como un peso fetal estimado bajo el percentil 10 asociado a un índice de pulsatilidad (IP) al Doppler de la arteria umbilical (AU) por debajo de dos desviaciones estándar del promedio. Se evaluaron cambios longitudinales, mortalidad y sobrevida perinatal. Resultados: Todos los parámetros tuvieron diferencias estadísticamente significativas en fetos RCIU. El índice de velocidad de flujo del istmo aórtico (IFI) y el índice de función miocárdico modificado (IFM-mod) mostraron los más evidentes cambios longitudinales y deterioro en el tiempo. Conclusiones: El IFI y el IFM-mod mostraron consistentes cambios longitudinales en fetos RCIU. Estos dos marcadores podrían ser usados junto a la medición del ductus venoso para evaluar el deterioro fetal y la indicación óptima del momento del parto.

Relação entre índice de resistência obtido pela ultra-sonografia Doppler transfortanela e o neurodesenvolvimento até o primeiro ano de vida em recém-nascidos a termo com encefalopatia hipóxico-isquêmica leve e moderada / Relation between the resistance index obtained by the transfontanellar Doppler ultrasonography and the neurological development until the first year of life in term infants with mild or moderate hypoxic-ischaemic encephalopathy

OBJETIVO: Avaliar a relação do índice de resistência (IR) obtido pela ultra-sonografia Doppler transfontanela com o neurodesenvolvimento até um ano de idade, em recém-nascidos (RN) a termo com encefalopatia hipóxica-isquêmica (EHI) leve a moderada, secundária à asfixia intra-parto. MÉTODO: Estudo prospectivo em 20 RN com EHI leve a moderada, IR elevado no primeiro exame de Doppler, e sem doenças associadas ou anormalidades morfológicas cerebrais. Foram realizados exames seriados bimensais de Doppler transfontanela a partir do sétimo dia de vida, e avaliações clínicas mensais do neurodesenvolvimento no primeiro ano de vida. RESULTADOS: Houve normalização progressiva dos valores de IR até o último exame realizado. Cinco pacientes apresentaram normalização clínico-neurológica no período neonatal, após o primeiro exame de Doppler. Quinze lactentes apresentaram alterações neurológicas com resolução a partir do segundo trimestre de vida. CONCLUSÃO: Houve relação entre os períodos em que ocorreu a normalização dos valores de IR e a melhora clínica-neurológica.

OBJECTIVE: To evaluate the relation between the resistance index (RI) obtained by transfontanellar Doppler ultrasonography, and the neurodevelopment until one year of life, at term newborns with mild or moderate hypoxic-ischaemic encephalopathy due to intrapartum asphyxia. METHOD: 20 term newborns, with mild or moderate hypoxic-ischemic encephalopathy, high values of resistance index in the first exam, and without cerebral morfologic abnormalities or other diseases. They were submitted to serial bimonthly transfontanellar Doppler ultrasonography, from the seventh day of life on, and monthly clinical neurodevelopment assessment until one year of life. RESULTS: There was a progressive normalization of RI values until the last examination. In five cases there were clinical neurologic normalization in the neonatal period after the first Doppler exam. Fifteen infants presented neurologic abnormalities, with normalization after the second trimester of life. CONCLUSION: There was a relation between the normal RI values with the normalization of the clinical assessment.

Ratio of middle cerebral to umbilical artery blood velocity in preeclamptic & hypertensive women in the prediction of poor perinatal outcome.

BACKGROUND & OBJECTIVES: Doppler velocimetry studies of placental and foetal circulation can provide important information regarding foetal well-being providing an opportunity to improve foetal outcome. The present study was undertaken to evaluate the role of middle cerebral to umbilical artery blood velocity waveform's systolic/diastolic ratio (MCA/UA) and biophysical profile as a predictor of perinatal outcome in hypertensive and preeclamptic pregnant women during the late third trimester. METHODS: Fifty preeclamptic pregnant women selected randomly in the last three weeks of the third trimester were stratified into two groups based on the MCA/UA ratio. All women were evaluated by foetal biophysical profile scoring. Thirty four women with foetal MCA/UA ratios > 1 and 16 with < or =1 were recruited in groups A and B respectively. The results of the ratio, and biophysical profile were evaluated with respect to the outcome of the infants and adverse perinatal outcome, defined as perinatal death, foetal cord blood gas analyses, cesarean delivery for foetal distress, admission to the neonatal intensive care unit, days in the neonatal intensive care unit (NICU) or low Apgar score. RESULTS: Rate of cesarean delivery was significantly (P<0.001) higher in group B than group A. There was a statistically significant increase in perinatal morbidity in B group. Apgar scores at 1 and 5 min were found to be lower in group B than group A. Umbilical cord blood partial oxygen pressure (pO2), partial carbon dioxide pressure (pCO2) was not different in the two groups; whereas, pH was lower in group B. In group A two neonates (5.9%) and in group B 12 neonates (75%) required admission in neonatal intensive care unit. Best cut-off levels of MCA, MCA/UA ratios were found to be 3 and 1, respectively. INTERPRETATION & CONCLUSION: The MCA/UA was valuable for predicting the outcome of preeclamptic and hypertensive pregnancies. When the ratio was <1, foetal prognosis was poor.

Transcranial Doppler evaluation of blood flow velocity changes in basal cerebral arteries in cerebral AVMs following embolisation and surgery.

Blood flow velocities in the basal cerebral arteries were evaluated in 41 patients with supratentorial arteriovenous malformation (AVM), using a transcranial doppler 64-B instrument. The AVM was surgically excised in 20 patients and embolised in 21 patients. Blood flow velocities in feeding basal cerebral arteries were found markedly decreased in both the groups, at 24 hours after intervention. On follow up study at 3 months, blood flow velocity in feeding cerebral artery was found to be increased in 47 percent of patients who were embolised, but remained normal in all the patients who underwent surgery.

Enfermedad vascular obstructiva neonatal / Occlusive vascular disease (neonatal stroke)

Introducción. La enfermedad vascular obstructiva neonatal puede ocurrir tanto en el feto como en el recién nacido. En el 50 por ciento de los casos la arteria cerebral media del lado izquierdo es la más afectada. La incidencia anual se reporta en 2.5 por cada 100,000 niños. Caso clínico. Lactante masculino de 3 meses de edad, producto de la primera gesta, de término, nació mediante cesárea con líquido amniótico claro, aparentemente sin datos de asfixia, ictericia o cianosis. Cursó asintomático hasta los 3 meses, cuando presentó crisis convulsivas localizadas a hemicuerpo derecho motivo por el cual es estudiado. Como hallazgo se encontró en el estudio de imagen un infarto antiguo a nivel del hemisferio izquierdo, en territorio de la arteria cerebral media con oclusión en su nacimiento. Conclusión. La incidencia de enfermedad vascular obstructiva en neonatos es más común de lo que se reporta, debido a su difícil reconocimiento al examen clínico. Los antecedentes perinatales y postnatales son importantes para la sospecha clínica y el estudio completo por medio de los diferentes métodos diagnósticos de gabinete; siendo la angiorresonancia la que ofrece una evaluación no invasiva del parénquima y de la vasculatura cerebral con mayor beneficio que la utilización de la angiografía

Embolización arterial múltiple secundaria a un mixoma en atrium izquierdo / Multiple arterial embolization following to left atrium myxoma

Se presenta un caso clínico de una mujer de 17 años de edad, con un mixoma en atrium izquierdo, que ocasionó embolización a las arterias cerebral, mesentérica superior e iliaca externa izquierda. Fue resuelto quirúrgicamente. La paciente tuvo evolución satisfactoria

Detecçåo da centralizaçåo do fluxo sangüíneo fetal através do doppler das artérias umbilical e cerebral média / Brain-sparing effect stage determination of fetal circulation by umbilical and middle cerebral arteries dopper ultrasound

O presente estudo teve como objetivos principais a verificaçåo, através do doppler das artérias umbilical e cerebral média, do fenômeno da centralizaçåo de fluxo fetal e o diagnóstico do crescimento intra-uterino retardado, em situaçöes de sofrimento crônico. Para tal, realizaram-se 102 exames em 55 gestantes de alto-risco com feto único, entre 30 e 40 semanas, utilizando o doppler colorido. Pôde-se nåo somente confirmar o fenômeno da redistribuiçåo de fluxo, com vasodilataçåo cerebral, como também verificar a existência de dois estágios do processo de centralizaçåo, "inicial e tardio". A "centralizaçåo tardia" associou-se em 100 por cento das vezes ao crescimento intra-uterino retardado

Indice umbílico-cerebral: novo parâmetro no diagnóstico do crescimento intra-uterino retardado / Umbilical-cerebral doppler ratio: a new parameter for the intrauterine growth retardation diagnosis

O presente estudo teve como objetivo principal a mensuraçåo do índice umbílico-cerebral, obtido a partir do doppler das artérias umbilical e cerebral média do feto, com vistas a verificar a capacidade preditiva desse índice no diagnóstico do crescimento intra-uterino retardado. Realizaram-se 102 exames em 55 gestantes de alto-risco com feto único, entre 30 e 40 semanas, utilizando-se doppler colorido. Quando se cotejou as duas artérias através da relaçåo entre os índices de pulsatilidade encontrados verificou-se que, em diferentes níveis de corte, o melhor resultado para a sensibilidade e especificidade foi para o valor menor ou igual a 0,9 como limete de normalidade. Acima dese valor se detectou a grande maioria dos fetos comprometidos (85 por cento), enquanto grande parte dos normais (82,9 por cento) teve resultado do índice abaixo desse limite. Destaca-se que a totalidade dos fetos que faziam centralizaçåo, todos com crescimento intra-uterino retardado, teve índice umbílico-cerebral maior que 0,9

Malformaciones arteriovenosas del lóbulo occipital / Medial occipital arteriovenous malformations

Se discute una serie quirúrgica de 15 malformaciones arteriovenosas (MAVs) del lóbulo occipital. Cada MAV estaba exclusiva o predominantemente alimentada por ramas de la arteria cerebral posterior (ACP). La edad media de los 8 hombres y las 7 mujeres en este grupo fuee de 26.1 años ( rango: 9-59 años). La hospitalización fue determinada por sangrado intracraneal espontáneo en ocho pacientes, convulsiones en cuatro, migraña recurrente en dos, y aumento de la presión intracraneal (debido a hidrocefalea asociada) en uno. Seis MAVs fueron grandes (dos sangraron), ocho fueron de tamaño mediano (cinco sangraron), y una fue pequeña (sangró). Mediante el empleo de técnica de microneurocirugía, catorce MAVs fueron extirpados completamente (un paciente requirió de dos craneotomías sucesivas para el logro de tal fin), y una, incompletamente. Una MAV fue obligadamente tratada por ligadura proximal de ramas de la ACP solamente, y, no sorpresivamente, un residuo muy importante fue demostrado mediante angiografía cerebral postoperatoria temprana. Este paciente, lamentablemente, falleció tres días después de la operación debido a broncoaspiración. Catorce pacientes sobrevivieron inicialmente a la operación. En un paciente se obtuvo un resultado postoperatorio pobre debido al "cataclismo de Spetzler y col." La paciente permaneció en estado vegetativo persistente hasta su muerte, la que ocurrió en otra clínica 5 meses después de la operación. Otro paciente murió de ventriculitis, meningitis y septicemia 3.5 meses después de la implantación de una derivación ventrículoperitoneal "prequirúrgica", complicaciones éstas no relacionadas con la extirpación completa de la MAV que fue llevada a cabo exitosamente una semana después del procedimiento derivativo. Todos los sobrevivientes quirúrgicos regresaron a sus ocupaciones previas a pesar de un defecto homónimo en su campo visual, que fue un hallazgo postoperatorio casi universal. Angiografía cerebral intraoperatoria fue realizada en cinco ocasiones. En una serie de 45 MAVs cerebrales intradurales operadas por el autor en un período de 18 años (que terminan en Diciembre de1986), 15 ocuparon el lóbulo occipital. Cada MAV correspondía a la variedad arteriovenosa en la clasificación histológica de McCormick1 y a los tipos I, II o III de la categorización angiográfica de Parkinson y Bachers.2 Veinte de estos pacientes de todas las edades, 19 juveniles con MAVs cerebrales arteriovenosas han sido previamente reportadas por el autor.3,4