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Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH.An experimental study was carried out.Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain).96 Wistar rats: 74 SAH and 22 sham intervention animals.Day 1: blood sampling, followed by the percutaneous injection of 100μl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals.Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT.Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83).The urotensinergic system is upregulated on day 5 in an experimental model of SAH.

Resumen Objetivo Evaluar si un modelo experimental de lesiones tipo masa (LM) transitoria en rata produce la liberacion precoz a sangre periferica de enolasa neuroespecifica (NSE) y proteina S100B como expresion del dano cerebral inducido. Diseno Estudio experimental con grupo control. Ambito Quirofano experimental del Instituto de Biomedicina (IBiS) del Hospital Universitario Virgen del Rocio. Participantes Catorce ratas adultas Wistar. Intervenciones Se extrajo muestra sanguinea basal y posteriormente se realizo: grupo LM, a traves de un trepano, se inflo el globo de una sonda con 500 μL/20 s; posteriormente, se realizaron 4 extracciones sanguineas cada 20 min. Grupo control, se repitieron de forma sistematica todos los pasos salvo que no se realizo trepano. Variables de interes principal Peso, mortalidad precoz, concentracion en suero de NSE y S100B. Resultados Encontramos diferencias entre las concentraciones de NSE y S100B a lo largo del tiempo dentro del propio grupo LM (p Conclusiones Las concentraciones en suero de NSE y S100B reflejan de forma precoz el dano cerebral que acontece sobre la sustancia gris y blanca en un modelo experimental de LM en rata.

The effects of human urotensin II (hUII) on the vascular tone of different animal species has been studied extensively. However, little has been reported on the vasoactive effects of rat urotensin (rUII) in murine models. The aim of the present study was to investigate the effects of rUII on vasoreactivity in rat basilar arteries. Basilar arteries from adult male Wistar rats (300-350 g) were isolated, cut in rings, and mounted on a small vessel myograph to measure isometric tension. rUII concentrations were studied in both resting and depolarized state. To remove endothelial nitric oxide effects from the rUII response, we treated selected arterial rings with Nω-nitro-L-arginine methyl ester (L-NAME). 10 μM rUII produced a potent vasoconstrictor response in rat basilar arteries with intact endothelium, while isometric forces remained unaffected in arterial rings treated with lower rUII concentrations. Although L-NAME did not have a significant effect on 10 μM rUII-evoked contraction, it slightly increased arterial ring contraction elicited by 1 μM rUII. In depolarized arteries, dose-dependent rUII increased depolarization-induced contractions. This effect was suppressed by L-NAME. Our results show that the rat basilar artery has a vasoconstrictor response to rUII. The most potent vasoconstrictor effect was produced by lower doses of rUII (0.1 and 1 μM) in depolarized arteries with intact endothelium. This effect could facilitate arterial vasospasm in vascular pathophysiological processes such as subarachnoid hemorrhage and hypertension, when sustained depolarization and L-type Ca(2+) channel activation are present.

Changes in Urotensin-II (U-II) concentration, a potent vasoconstrictor peptide, have been detected in various pathologies, but it has been impossible to define a normality range. We aimed to analyze the concordance and interchangeability between two enzyme immunoassay methods developed by Phoenix Pharmaceuticals, Inc. to measure U-II plasma concentration in rats: ELISA and fluorescent EIA. Assays resulted positively correlated (r = 0.850; p < 0.01). There was a significant difference between assays values (p < 0.001). The analysis of agreement (Bland and Altman plot) stated that the mean of the differences was 2.055 (SD ± 0.588). Hence, we concluded that the two U-II assays were correlated but not interchangeable.

Objetivo: Establecer el valor predictivo, para desarrollar deterioro neurológico tardío de origen isquémico (DNI), de un estudio doppler transcraneal (DTC) en pacientes con hemorragia subaracnoidea espontánea (HSA) en buena situación neurológica. Diseño: Estudio descriptivo-observacional desarrollado durante 3 años. Ámbito: Cuidados Críticos y Urgencias. Pacientes: Se incluyeron de forma consecutiva aquellos pacientes con HSA en buena situación neurológica (Hunt-Hess I-III). Variables de Interés: DNI (disminución en 2 puntos del GCS o déficit focal), velocidad media (VM) en arterias cerebrales medias, índice de Lindegaard (IL). Se consideró patrón sonográfico de vasoespasmo (PSV) cuando la VM fue>120cm/s y existía un IL>3. Resultados: La media de edad de los 122 pacientes fue de 54,1±13,7 años. El 57,3% eran mujeres. Se detectaron 24 pacientes con PSV (19,7%) encontrándose VM elevadas en 38 pacientes (31,1%). 21 pacientes desarrollaron DNI (VM 183+/-49cm/s), todos presentaron PSV. En los pacientes con DNI se detectó un aumento de VM de 22+/-5cm/s/24h durante los 3 primeros días. Al comparar aquellos pacientes que no presentaron VM elevadas (85 pacientes/VM 67+/-16,6cm/s) con respecto a los que desarrollaron DNI encontramos diferencias en las VM (p

La microdiálisis cerebral, introducida en estudios experimentales hace unos 40 años, ha sido empleada en la clínica desde 1992 para la monitorización neuroquímica de pacientes en unidades de cuidados intensivos. Los principios en los que se basa esta técnica se encuentran íntimamente ligados al metabolismo cerebral. El estudio de los metabolitos detectados en el intersticio tisular cerebral, a través de la membrana semipermeable de la que dispone el dispositivo, permite estimar la situación de las distintas rutas metabólicas fisiológicas cerebrales, analizando las modificaciones que se producen cuando estas tornan hacia rutas menos eficientes desde el punto de vista energético y detectando productos de desecho secundarios a la lesión tisular. A pesar de sus limitaciones actuales, esta técnica aporta información relevante para la investigación y el abordaje clínico de los pacientes neurocríticos. Cerebral microdialysis, introduced in experimental studies 40 years ago, has been used clinically since 1992 for the neurochemical monitoring of patients in intensive care. The principles underlying this technique are closely related to brain metabolism. The study of the metabolites detected at brain interstitial tissue level, through the semipermeable membrane of the device, allows us to assess different physiological pathways in the brain, analyzing the changes that occur when they become less efficient in terms of energy, and also detecting waste products secondary to tissue damage. Despite its current limitations, this technique provides relevant information for research and the clinical management of critical neurological patients.

This study tested the hypothesis that S100β is a useful screening tool for detecting intracranial lesion (IL) in patients with a normal level of consciousness after traumatic brain injury (TBI).One hundred and forty-three post-TBI patients without a decrease in consciousness (GCS = 15) and with at least one neurological symptom (e.g. transitory loss of consciousness, amnesia, headache, dizziness or vomiting) were prospectively included. A blood sample was drawn at 6-hours post-TBI. A routine CT scan was obtained within 24 hours post-injury. Diagnostic properties of S100β for IL prediction in CT scan findings were tested using ROC-analysis.A total of 15 patients (10.5%) had IL. Serum levels were significantly higher in these patients. Significant differences were found between S100β levels and CT scan findings (p = 0.007). ROC-analysis showed that S100β is a useful tool for detecting the presence of IL in CT scans (p = 0.007). In this series, the best cut-off for S100β is 0.130 µg L(-1), with 100% sensitivity and 32.81% specificity.Within the first 6 hours post-TBI, serum S100β seems to be an effective biochemical indicator of IL in patients without a decrease in consciousness. These results indicate that higher S100β cut-off values substantially improve the clinical relevance of this protein.

To study the predictive capacity of early S100beta samples for long-term outcome prediction after severe TBI.Eighty-seven patients with severe TBI were studied. Clinical and CT scan were taken at admission. S100beta concentration was quantified at admission and 24, 48 and 72 hours post-TBI (days 0, 1, 2 and 3). Outcome was assessed 12 months after discharge using Glasgow Outcome Score (GOS).Significant negative correlations were found between 1-year GOS and S100beta concentrations on days 1-3, but not on day 0. Deceased patients showed higher S100beta concentration than survivors on days 1-3. Good (GOS = 4-5) vs poor outcome (GOS = 1-3) differed significantly on day 3. Death outcome was independently predicted by day 2 (2.37 microg l(-1)), day 3 (1.41 microg l(-1)) samples and absence of pupillary reaction. Poor outcome was predicted independently only by pupillary reaction and the 72-hour sample (1.1 microg l(-1)), but this predictive model was less satisfactory than the predictive model for death.A temporal profile of S100beta release from admission to 72 hours post-TBI is strongly recommended for use in identifying patients at risk of developing a worse outcome. The S100beta protein might be an early biomarker for predicting long-term outcome in patients with acute severe TBI.

To explore the possibility of identifying skull fracture, with or without clinical signs, as a predictor of positive CT scans in mild traumatic brain injury (mTBI).Prospective cohort study, matched 1:1 for five potential confounding variables (age, sex, symptoms, mechanism of injury and extracranial trauma severity).The study was performed on patients with mTBI (Glasgow Coma Scale 15-14), with or without radiologically demonstrated skull fracture. The cohort with skull fracture included 155 patients selected from a sample of 5097 mTBI patients treated during 1998 at the Critical Care and Emergency Department of the Trauma Centre. The cohort without skull fracture was prospectively recruited from patients with mTBI treated in the same department from 2002-2005.The percentage of patients with intracranial lesion (IL) was significantly higher in mTBI patients with skull fracture than in those without. The risk of requiring neurosurgery was 5-fold higher when skull fracture was present. Of mTBI patients with skull fracture and IL, 63.2% showed no clinical signs of bone injury.Skull fracture, with or without clinical signs, in mTBI patients is associated with an increased risk of neurosurgically-relevant intracranial lesion.

We have previously described that L-type Ca(2+) channels' (LTCCs) activation and metabotropic Ca(2+) release from the sarcoplasmic reticulum (SR) regulate RhoA/Rho kinase (ROCK) activity and sustained arterial contraction. We have investigated whether this signaling pathway can be altered in a new experimental model of subarachnoid hemorrhage (SAH). For this purpose, arterial reactivity was evaluated on days 1 to 5 after surgery. A significant increase of basal tone, measured 4 and 60min after normalization, was observed on day 5 after SAH and at 60min on days 2 and 3 after SAH. This phenomenon was suppressed with LTCCs and ROCK inhibitors. We have also studied arterial rings vasoreactivity in response to high K(+) solutions. Interestingly, there were no significant differences in the phasic component of the high K(+)-induced contraction between sham and SAH groups, whereas a significant increase in the sustained contraction was observed on day 5 after SAH. This latter component was sensitive to fasudil, and selectively reduced by low nifedipine concentration, and phospholipase C and SR-ATPase inhibitors. Therefore, our data suggest that the metabotropic function of LTCCs is potentiated in SAH. Our results could provide a new strategy to optimize the pharmacological treatment of this pathological process.

Secondary brain insults predominantly due to hypotension are frequent among patients with fatal traumatic brain injury. We assessed the correlation between different systemic secondary brain insults and brain death in 404 patients admitted to our intensive care unit (ICU) after severe traumatic brain injury. We collated data on hypoxemia and hypotension prior to as well as the occurrence of hypoxemia, hypotension, shock, anemia, hyperglycemia, and hyperthermia within the first 24 hours after ICU admission. We also considered both the presence of extracranial injuries and the category of traumatic brain injury using computerized tomography. The 59 patients (14.6%) who developed brain death, were significantly older than patients without a fatal neurological outcome (46.1 +/- 22 vs 29.5 +/- 14.9 years; P < .0001). Intracranial mass lesions, whether surgically evacuated were more frequent among brain-dead patients. The systemic secondary brain insults significantly associated with brain death were hypoxemia, hypotension, shock, anemia, and hyperglycemia within the first 24 hours after ICU admission. After multivariate analysis, the factors that independently predicted brain death were the occurrence of shock (odds ratio [OR], 6.74; 95% confidence interval [CI], 2.85-15.84; P = .001) and older age (OR, 1.05; 95% CI, 1.03-1.07; P = .003). In conclusion, early shock seems to be the major systemic secondary brain insult associated with brain death in patients with severe traumatic brain injury. Prevention of or correction of shock might help to either decrease the occurrence of a fatal neurological outcome or in brain-dead patients to preserve organs in better condition for procurement.

Objetivo: Establecer el valor predictivo, para desarrollar deterioro neurológico tardío de origen isquémico (DNI), de un estudio doppler transcraneal (DTC) en pacientes con hemorragia subaracnoidea espontánea (HSA) en buena situación neurológica. Diseño: Estudio descriptivo-observacional desarrollado durante 3 años. Ámbito: Cuidados Críticos y Urgencias. Pacientes: Se incluyeron de forma consecutiva aquellos pacientes con HSA en buena situación neurológica (Hunt-Hess I-III). Variables de Interés: DNI (disminución en 2 puntos del GCS o déficit focal), velocidad media (VM) en arterias cerebrales medias, índice de Lindegaard (IL). Se consideró patrón sonográfico de vasoespasmo (PSV) cuando la VM fue>120cm/s y existía un IL>3. Resultados: La media de edad de los 122 pacientes fue de 54,1±13,7 años. El 57,3% eran mujeres. Se detectaron 24 pacientes con PSV (19,7%) encontrándose VM elevadas en 38 pacientes (31,1%). 21 pacientes desarrollaron DNI (VM 183+/-49cm/s), todos presentaron PSV. En los pacientes con DNI se detectó un aumento de VM de 22+/-5cm/s/24h durante los 3 primeros días. Al comparar aquellos pacientes que no presentaron VM elevadas (85 pacientes/VM 67+/-16,6cm/s) con respecto a los que desarrollaron DNI encontramos diferencias en las VM (p120cm/sc and IL>3. Results: The mean age of the 122 patients was 54.1±13.7 years; 57.3% were women. SVP was detected in 24 patients (19.7%), although high velocities patterns (HVP) were present in 38 patients (31.1%). DCI developed in 21 patients (MV183+/-49cm/sc), all with previous SVP. In this group MV increased 22+/-5cm/sc/day during the first 3 days. The group without HVP (84 patients/MV of 67+/-16.6cm/sc), compared with DCI group, showed differences in highest MV (p

Una de las causas principales de lesion cerebral secundaria es la hipoxia cerebral, fundamentalmente de origen isquemico. No obstante, la oxigenacion tisular cerebral depende de multiples variables fisiologicas y la hipoxia cerebral puede ser originada por una alteracion de cualquiera de ellas. Aunque han sido desarrollados varios metodos de monitorizacion continua de la oxigenacion cerebral en pacientes neurocriticos, la medicion directa y continua de la presion de oxigeno en el tejido cerebral (PtiO2) es una realidad en el manejo de pacientes neurocriticos desde los ultimos anos. Esta tecnica destaca por su fiabilidad y valor de la informacion que proporciona. En el presente articulo se expone una revision de los aspectos mas relevantes de la monitorizacion de la PtiO2 y se propone un protocolo para su interpretacion. Este algoritmo pretende facilitar la identificacion de diferentes tipos de hipoxia cerebral y la correcta eleccion terapeutica en el complejo proceso de toma de decisiones en pacientes neurologicos criticos en riesgo de hipoxia cerebral.

The objective was to determine whether the age of patients with mild head injury and skull fracture influences the level of risk for acute intracranial injuries.A study was conducted of 156 patients with skull fracture, 60 children (aged14 years) and 96 adults, detected among 5,097 consecutive patients with mild head injury (Glasgow Coma Scale [GCS] score of 15-14 points) arriving at the Emergency Department of a Level I University Hospital Trauma Center during 1998. Acute intracranial injuries were defined as traumatic brain injuries identified by cranial computed tomography scan, excluding pneumocephalus.Compared with the children, this risk of intracranial injury was 13 times greater in the adults aged 14-54 years and 16 times greater in the over-54-year-olds. Besides age over 14 years (p0.0001), compound skull fracture (p0.001), and a GCS score of 14 (p0.001) were factors significantly associated with intracranial injury in the logistic regression analysis.Skull fracture in mild head injury implies a greater risk of intracranial injury in adults than in children.

Objective: Describe the results obtained with a new percutaneous, intracisternal model of Subarachnoid Haemorrhage (SAH) in Wistar rats by a single injection of non-heparinised, autologous blood. Methods: Once anaesthetized the rat was fixed prone in a stereotaxic frame. After identifying the projection of the occipital bone, the needle of the stereotaxic frame aspirated towards the foramen magnum until it punctured through the atlanto-occipital membrane and obtained cerebrospinal fluid. Autologous blood (100. μl) was withdrawn from the tail and injected intracisternally. This procedure was repeated in the sham group, injecting 100. μl of isotonic saline. On the fifth day post-intervention, the rats were anaesthetized and the brain was exposed. After a lethal injection of ketamine the brain was explanted and fixed in paraformaldehyde. Gross and microscopic inspection of the slices revealed the existence or non-existence of pathological findings. Results: A total of 26 rats were operated on (13 in the SAH group/13 in the sham group). The average time between obtaining the blood and the start of the intracisternal injection was 10 (±1.2). s. The mortality rate was 16.12%. Intra- and extraparenchymal ischemic-haemorrhagic lesions were found in three animals (23.07%) - all from the SAH group - with ischemic neuronal cell injury detected in two of the three. Conclusions: The new murine model of SAH is easy to perform, with low mortality, minimally invasive, which makes it interesting for future studies on vasospasm-related delayed SAH complications. © 2012 Elsevier B.V., This study has been funded by Health Research Fund 2010 (Fondos de Investigación Sanitaria, FIS 2010) from the Instituto de Salud Carlos III, Spain.

Objetivo. Investigar nuestras practicas clinicas, a fin de identificar oportunidades de mejora en el manejo medicoquirurgico de las hemorragias subaracnoideas (HSA) espontaneas. Pacientes y metodos. Estudio de cohortes, longitudinal, prospectivo, de las HSA atendidas consecutivamente en los servicios de cuidados criticos y urgencias de 29 hospitales publicos de Andalucia durante 20 meses, de 2000 a 2002. Se consideraron HSA los accidentes cerebrovasculares hemorragicos agudos con este diagnostico tomografico. Se analizaron los resultados a 12 meses y el manejo asistencial (terapeutica medica y quirurgica, tecnicas diagnosticas, tiempos asistenciales y complicaciones neurologicas especificas), comparandolo con las practicas clinicas que la evidencia cientifica ha demostrado de mayor utilidad. Se catalogaron como muertes potencialmente evitables los obitos por resangrado en pacientes sin estudio arteriografico o sin exclusion del aneurisma. Resultados. Se incluyeron 506 HSA. Se perdio durante el seguimiento el 5% de la muestra. Fallecieron 155 enfermos. Las variables no modificables de riesgo independiente para la mortalidad fueron: edad, genero masculino, antecedente de hipertension arterial, coma a la recepcion hospitalaria e hidrocefalia. Las variables influenciables de riesgo independiente para fallecer resultaron ser: ausencia de analgesia urgente, carencia de diagnostico arteriografico, aparicion de deterioro neurologico isquemico y resangrado. El 20% de la mortalidad global podria considerarse potencialmente evitable. Conclusiones. Aunque la letalidad es mayoritariamente dependiente de variables medicamente no influenciables (sexo, edad, antecedentes, gravedad clinica e hidrocefalia), los decesos, en un 20%, estan asociados a factores modificables.

Objetivo. Valorar la incidencia y resultados de las hemorragias subaracnoideas (HSA) espontaneas en Andalucia. Pacientes y metodos. Estudio longitudinal, prospectivo, de las HSA asistidas en 28 hospitales de Andalucia, durante tres meses del ano 2000. Se consideraron HSA los ictus hemorragicos agudos con este diagnostico tomografico. La incidencia bruta (TB) se establecio mediante la informacion censal del Instituto Andaluz de Estadistica. Las tasas estandarizadas (TEE) se estimaron con relacion a la poblacion europea. Los resultados se valoraron al alta hospitalaria segun el GOS (del ingles, Glasgow Outcome Score) y a los 12 meses, segun el indice de Barthel (IB). Resultados. La TB por 100.000 habitantes/ano se situo en 5,7 casos y la TEE en 5,8. La comparacion de incidencias segun provincia o sexo no mostro diferencias estadisticamente significativas. El periodo de maximo riesgo corresponde al intervalo 55-74 anos (TB: 14,1). La TB y TEE de letalidad aguda coincidio en 1,5. A los 12 meses, la TB y TEE de letalidad ascendio a 1,9 por 100.000 habitantes y ano. La mortalidad se concentro de forma estadisticamente significativa (p< 0,01) entre los mayores de 65 anos; no influyo el sexo, pero si la gravedad clinica (p< 0,001) y la cuantia del sangrado (p< 0,005). Conclusiones. La incidencia de las HSA espontaneas en Andalucia se situa en tasas medias. La proporcion de resultados desfavorables es elevada, aunque similar a la de otras series. La letalidad se asocia significativamente a factores (edad, gravedad clinica y volumen de sangrado) no modificables medicamente

Objective: To report new strategies in the treatment of persistent memory deficits following traumatic brain injury (TBI) using a combination of pharmacology and neuropsychological training. Study design: Two studies were carried out. The first study measured the regional cerebral blood flow (rCBF) of seven Patients with TBI with very severe memory deficits, once while resting and once one hour after the administration of citicholine (CDPc). In the second study, two groups of five patients of the same characteristics underwent an ecological neuropsychological memory rehabilitation program; during which time, one group was administered a placebo (Group A), and the other received CDPc (1~g/d v.o.) (Group B). Results: The results of Experiment 1 showed a hypoperfusion of the inferior left temporal cerebral blood flow during rest state while an induced normalization was observed after administration of the drug. Results of Experiment 2 showed no improvements in Group A's neuropsychological functions, while memory, learning processes and verbal fluency of Group B improved significantly after treatment. Conclusions: CDP-choline seems to be a drug with special affinity for cerebral areas associated with memory acting just where needed, normalizing blood flow in the hypoperfused left temporo-basal region, and making neuropsychological training effective. In general, data suggests that cognitive rehabilitation would follow the principle of first restoring and maintaining cerebral blood flow in the lesional site and then exercising function. In this study on memory rehabilitation, memory recuperation was made possible by first normalizing blood flow at the lesional site and at the same time applying neuropsychological training.