RESUMEN
BACKGROUND AND PURPOSE: Information of collateral flow may help to determine eligibility for thrombectomy. Our aim was to identify CT perfusion-based surrogate parameters of good collateral status in acute anterior circulation ischemic stroke. MATERIALS AND METHODS: In this retrospective study, we assessed the collateral status of 214 patients who presented with acute ischemic stroke due to occlusion of the MCA M1 segment or the carotid terminus. Collaterals were assessed on dynamic CTA images analogous to the multiphase CTA score by Menon et al. CT perfusion parameters (time-to-maximum, relative CBF, hypoperfusion intensity ratio, and CBV-index) were assessed with RAPID software. The Spearman rank correlation and receiver operating characteristic analyses were performed to identify the parameters that correlate with collateral scores and good collateral supply (defined as a collateral score of ≥4). RESULTS: The Spearman rank correlation was highest for a relative CBF < 38% volume (ρ = -0.66, P < .001), followed by the hypoperfusion intensity ratio (ρ = -0.49, P < .001), CBV-index (ρ = 0.51, P < .001), and time-to-maximum > 8 seconds (ρ = -0.54, P < .001). Good collateral status was better identified by a relative CBF < 38% at a lesion size <27 mL (sensitivity of 75%, specificity of 80%) compared with a hypoperfusion intensity ratio of <0.4 (sensitivity of 75%, specificity of 62%), CBV-index of >0.8 (sensitivity of 60%, specificity of 78%), and time-to-maximum > 8 seconds (sensitivity of 68%, specificity of 76%). CONCLUSIONS: Automated CT perfusion analysis allows accurate identification of collateral status in acute ischemic stroke. A relative CBF < 38% may be a better perfusion-based indicator of good collateral supply compared with time-to-maximum, the hypoperfusion intensity ratio, and the CBV-index.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Circulación Cerebrovascular , Circulación Colateral , Humanos , Perfusión , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
PURPOSE: We hypothesize that the detectability of early ischemic changes on non-contrast computed tomography (NCCT) is limited in hyperacute stroke for both human and machine-learning based evaluation. In short onset-time-to-imaging (OTI), the CT angiography collateral status may identify fast stroke progressors better than early ischemic changes quantified by ASPECTS. METHODS: In this retrospective, monocenter study, CT angiography collaterals (Tan score) and ASPECTS on acute and follow-up NCCT were evaluated by two raters. Additionally, a machine-learning algorithm evaluated the ASPECTS scale on the NCCT (e-ASPECTS). In this study 136 patients from 03/2015 to 12/2019 with occlusion of the main segment of the middle cerebral artery, with a defined symptom-onset-time and successful mechanical thrombectomy (MT) (modified treatment in cerebral infarction score mTICIâ¯= 2c or 3) were evaluated. RESULTS: Agreement between acute and follow-up ASPECTS were found to depend on OTI for both human (Intraclass correlation coefficient, ICCâ¯= 0.43 for OTIâ¯< 100â¯min, ICCâ¯= 0.57 for OTI 100-200â¯min, ICCâ¯= 0.81 for OTIâ¯≥ 200â¯min) and machine-learning based ASPECTS evaluation (ICCâ¯= 0.24 for OTIâ¯< 100â¯min, ICCâ¯= 0.61 for OTI 100-200â¯min, ICCâ¯= 0.63 for OTIâ¯≥ 200â¯min). The same applied to the interrater reliability. Collaterals were predictors of a favorable clinical outcome especially in hyperacute stroke with OTIâ¯< 100â¯min (collaterals: ORâ¯= 5.67 CIâ¯= 2.38-17.8, pâ¯< 0.001; ASPECTS: ORâ¯= 1.44, CIâ¯= 0.91-2.65, pâ¯= 0.15) while ASPECTS was in prolonged OTIâ¯≥ 200â¯min (collaterals ORâ¯= 4.21,CIâ¯= 1.36-21.9, pâ¯= 0.03; ASPECTS: ORâ¯= 2.85, CIâ¯= 1.46-7.46, pâ¯= 0.01). CONCLUSION: The accuracy and reliability of NCCT-ASPECTS are time dependent for both human and machine-learning based evaluation, indicating reduced detectability of fast stroke progressors by NCCT. In hyperacute stroke, collateral status from CT-angiography may help for a better prognosis on clinical outcome and explain the occurrence of futile recanalization.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Isquemia Encefálica/terapia , Angiografía Cerebral/métodos , Angiografía por Tomografía Computarizada/métodos , Humanos , Aprendizaje Automático , Pronóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND AND PURPOSE: Endovascular embolization using liquid embolic agents is a safe and effective treatment option for AVMs and dural arteriovenous fistulas. The aim of this study was to assess the degree of artifact inducement by the most frequently used liquid embolic agents in conventional CT in an experimental in vitro model. MATERIALS AND METHODS: Dimethyl-sulfoxide-compatible tubes were filled with the following liquid embolic agents (n = 10, respectively): Onyx 18, all variants of Squid, PHIL 25%, PHIL LV, and n-BCA mixed with iodized oil. After inserting the tubes into a CT imaging phantom, we acquired images. Artifacts were graded quantitatively by the use of Hounsfield units in a donut-shaped ROI using a customized software application that was specifically designed for this study and were graded qualitatively using a 5-point scale. RESULTS: Quantitative and qualitative analyses revealed the most artifacts for Onyx 18 and the least artifacts for n-BCA, PHIL 25%, and PHIL LV. Squid caused more artifacts compared with PHIL, both for the low-viscosity and for the extra-low-viscosity versions (eg, quantitative analysis, Squid 18: mean ± SD, 30.3 ± 9.7 HU versus PHIL 25%: mean ± SD, 10.6 ± 0.8 HU; P < .001). Differences between the standard and low-density variants of Squid were observed only quantitatively for Squid 12. There were no statistical differences between the different concentrations of Squid and PHIL. CONCLUSIONS: In this systematic in vitro analysis investigating the most commonly used liquid embolic agents, relevant differences in CT imaging artifacts could be demonstrated. Ethylene-vinyl alcohol-based liquid embolic agents induced more artifacts compared with liquid embolic agents that use iodine as a radiopaque component.
Asunto(s)
Artefactos , Embolización Terapéutica , Fantasmas de Imagen , Tomografía Computarizada por Rayos X , Dimetilsulfóxido , Combinación de Medicamentos , Embolización Terapéutica/métodos , Técnicas In Vitro , Polivinilos , Tantalio , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND AND PURPOSE: Treatment of ruptured blister-like aneurysms is technically challenging. This study aimed at analyzing the safety and efficacy of the Flow-Redirection Endoluminal Device (FRED) in the treatment of ruptured blister-like aneurysms. MATERIALS AND METHODS: In a retrospective multicenter study, all patients treated with the FRED due to a ruptured intracranial blister-like aneurysm between January 2013 and May 2019 were analyzed. The primary end points for clinical safety were mRS 0-2 at 6 months after treatment and the absence of major ipsilateral stroke or death. The primary end points for efficacy were the absence of rebleeding after treatment and complete angiographic occlusion according to the O'Kelly-Marotta classification at 6 months after treatment. RESULTS: In total, 30 patients with 30 ruptured blister-like aneurysms were treated. Immediate complete aneurysm obliteration (O'Kelly-Marotta classification D) with the FRED was achieved in 10 patients (33%). Of the 26 patients with follow-up, complete obliteration was achieved in 21 patients (80%) after 6 months and in 24 patients (92%) in the final follow-up (median, 22 months). Twenty-three patients (77%) achieved mRS 0-2 at 6 months. Major stroke or death occurred in 17%. Two patients died due to pneumonia, and 2 patients died due to infarction following cerebral vasospasm. There was no case of rebleeding after FRED implantation. There was 1 case of delayed asymptomatic stent occlusion. CONCLUSIONS: Treatment of ruptured blister-like aneurysms with the FRED is safe and effective.
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Aneurisma Roto/cirugía , Procedimientos Endovasculares/instrumentación , Aneurisma Intracraneal/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Although patient-centredness is considered a key component of high-quality neurological care, it is unclear to what extent it can or should be implemented during the acute phase. Using acute stroke as an example, the aim was to identify critical junctures for patient-centredness along the acute care pathway from the perspectives of patients, relatives and staff. METHODS: A qualitative multi-method study was conducted including 27 non-participant observations and 37 semi-structured interviews with patients, relatives and staff. Junctures were defined as critical when mentioned (as problematic) in two or three information sources (i.e. observations, staff interviews, or patient and relative interviews), as potentially critical when mentioned in one, and as uncritical when not mentioned. RESULTS: Post-procedure communication after thrombectomy, patients' stay at the stroke unit and decision-making around transfer, discharge and rehabilitation were identified as critical junctures for patient-centredness. Arrival at the emergency department and the (thrombectomy) treatment itself were identified as uncritical junctures, whilst history-taking and treatment preparation, the treatment decision and patients' stay at the intensive care unit were identified as potentially critical junctures. CONCLUSIONS: In acute stroke care, patients, relatives and staff prioritize fast over patient-centred decision-making in the most time-critical phases, especially before and during treatment. This is reversed after the procedure, when difficulties arise implementing a patient-centred approach in clinical practice. To improve patient-centredness where it is most needed, clear guidelines and accessible resources are recommended. Future research should investigate whether insights from acute phases of stroke care are applicable to other neurological conditions as well.
Asunto(s)
Atención Dirigida al Paciente , Accidente Cerebrovascular , Cuidados Críticos , Humanos , Investigación Cualitativa , Calidad de la Atención de Salud , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND AND PURPOSE: Endovascular embolization can be an effective treatment for cranial dural arteriovenous fistulas. However, a considerable number of dural arteriovenous fistulas still cannot be treated sufficiently. The purpose of this study was to report our single-center experience of endovascular embolization of dural arteriovenous fistulas with Onyx, including the investigation of the influence of angioarchitectural features on the treatment success. MATERIALS AND METHODS: Clinical data, angioarchitectural features, complications, treatment success (defined as complete symptom remission for low-grade dural arteriovenous fistulas and complete occlusion for high-grade dural arteriovenous fistulas), and occlusion rates were assessed. The influence of various angioarchitectural features (including location, pattern of venous drainage, and quantity and origin of feeding arteries) was investigated using multivariable backward logistic regression. RESULTS: One hundred four patients with 110 dural arteriovenous fistulas were treated in 132 treatment procedures. Treatment success and complete occlusion rates were 81.8% and 90.9%, respectively. After a mean follow-up of 23.6 months, 95.5% of the patients showed complete symptom remission or symptom relief. The overall complication rate was 8.3% (4.5% asymptomatic, 2.3% transient, and 1.5% permanent complications). Logistic regression showed that ≥10 feeding arteries (P = .041) and involvement of the ascending pharyngeal artery (P = .039) significantly lowered the probability of treatment success. Treatment success tended to be lower for low-grade dural arteriovenous fistulas, Cognard type I dural arteriovenous fistulas, and dural arteriovenous fistulas with involvement of dural branches of the internal carotid artery, however without reaching statistical significance in the multivariable model. CONCLUSIONS: The presence of multiple feeding arteries and involvement of the pharyngeal artery negatively influence the treatment success of endovascular embolization of cranial dural arteriovenous fistulas with Onyx.
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Malformaciones Vasculares del Sistema Nervioso Central/patología , Malformaciones Vasculares del Sistema Nervioso Central/terapia , Embolización Terapéutica/métodos , Polivinilos/uso terapéutico , Adulto , Anciano , Procedimientos Endovasculares/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: We aimed to analyze the clinical outcome after mechanical thrombectomy in patients with premorbid mRS 3 and 4 because there are currently no data on this patient group. MATERIALS AND METHODS: Between January 2009 and November 2017, all patients with premorbid mRS 3 or 4 undergoing mechanical thrombectomy due to anterior circulation stroke were selected. Good outcome was defined as a clinical recovery to the status before stroke onset (ie, equal premorbid mRS and mRS at 90 days). In addition, mortality at discharge and at 90 days was analyzed. RESULTS: One hundred thirty-six patients were included, of whom 81.6% presented with premorbid mRS 3; and 18.4%, with premorbid mRS 4; 24.0% of patients with premorbid mRS 4 achieved clinical recovery compared with 20.7% of patients with premorbid mRS 3 (P = .788). However, the proportion of hospital mortality and mortality at 90 days was nonsignificant, but markedly higher in patients with premorbid mRS 4. Multivariate analysis identified low NIHSS scores (OR, 0.92; 95% CI, 0.85-0.99; P = .040), high ASPECTS (OR, 1.45; 95% CI, 1.02-2.16; P = .049), and TICI 2b-3 (OR, 7.11; 95% CI, 1.73-49.90; P = .017) as independent predictors of good outcome. CONCLUSIONS: Good outcome in patients with premorbid mRS 3 and 4 is less frequent compared with premorbid mRS 0-2. Nevertheless, about 20% of the patients return to their premorbid mRS, which may justify endovascular treatment. The most important predictor of good outcome is successful recanalization.
Asunto(s)
Accidente Cerebrovascular/cirugía , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/etiología , Trombectomía/efectos adversos , Resultado del TratamientoRESUMEN
Agomelatine is a new antidepressant drug acting as an antagonist of 5-hydroxytryptamine receptor 2C (5-HTR2C) and agonist of melatonergic receptors 1 and 2 (MT1 and MT2). Because of this dual action, it is an atypical antidepressant. The aim of this study was to investigate chronic anticonvulsant effects of agomelatine on penicillin-induced epilepsy model. Adult male Sprague-Dawley rats divided into four groups and were administered with tap water (vehicle), and agomelatine doses of 10 mg/kg, 50 mg/kg and 100 mg/kg for 14 days via oral gavage. After the last doses were given, epileptic seizures were induced by intracortical penicillin (500 IU/2.5 µl) application in rats under urethane (1.25 g/kg intraperitoneal) anesthesia. Electrocorticogram (ECoG) recordings were obtained from the somatomotor cortex through 90 min, and spike frequencies and amplitudes were analyzed. The spike frequency analyses revealed that only 50 mg/kg agomelatine administration decreased the spike frequencies of hypersynchronous discharge of neurons caused by penicillin (p < 0.05). No significant differences in amplitudes between experimental groups were observed. In addition, mRNA expressions of vesicular glutamate transporter 1 (VGLUT1) and vesicular gamma-aminobutyric acid transporter (VGAT) in response to the agomelatine active dose, 50 mg/kg, showed no significant effect of agomelatine on the mRNA expression. Our results indicate that chronic treatment with agomelatine may have potential anticonvulsant effects. Agomelatine may be a promising drug for epilepsy patients having depression due to its antiepileptic and antidepressant effects.
Asunto(s)
Acetamidas/farmacología , Electrocorticografía/efectos de los fármacos , Penicilinas/farmacología , Convulsiones/prevención & control , Animales , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Masculino , Microinyecciones , Corteza Motora/metabolismo , Corteza Motora/fisiopatología , Ratas , Convulsiones/inducido químicamente , Convulsiones/fisiopatología , Proteína 1 de Transporte Vesicular de Glutamato/biosíntesis , Proteínas del Transporte Vesicular de Aminoácidos Inhibidores/biosíntesisRESUMEN
Resveratrol (3,5,4'-stilbenetriol), a natural polyphenol produced by various plants, has attracted attention over the past decade because of its multiple beneficial properties, including anti-inflammatory, anti-oxidant and chemopreventive, yet, there is limited information about its antiepileptic effects. Moreover, its poor solubility in water and low bioavailability are the challenging issues. In the present study, we aimed to investigate effects of free resveratrol and resveratrol delivered in amphipathic liposomal delivery system, which has a high blood-brain barrier crossing potential, on penicillin-induced epileptic seizure model. For this purpose, adult male Sprague-Dawley rats were divided into four groups as saline (Control), liposome (LIP), free resveratrol (RES) and resveratrol+liposome (RES+LIP). Penicillin-induced epileptic activity was recorded for 120 min by electrocorticography. Glutathione S-transferase (GST), Glutathione (GSH), Superoxide dismutase (SOD) and Malondialdehyde (MDA) assays were performed in brain tissues collected. Our results showed that RES+LIP was the most effective anticonvulsant treatment on penicillin-induced epileptic seizures when compared to control, as RES+LIP immediately decreased the number of spikes per minute. GST and SOD activity, as well as the GSH levels, were significantly increased in the RES+LIP group as compared with the control group. Also, the MDA levels were significantly higher in the RES+LIP compared to RES and control groups. In conclusion, RES+LIP treatment was more effective on the decrease in spike frequency and spike amplitudes than other treatments. Our results suggest that the RES+LIP is more effective than RES on penicillin-induced epileptiform activity.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Portadores de Fármacos , Epilepsia/tratamiento farmacológico , Liposomas , Estilbenos/administración & dosificación , Animales , Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Electrocorticografía , Epilepsia/metabolismo , Glutatión/metabolismo , Glutatión Transferasa/metabolismo , Masculino , Malondialdehído/metabolismo , Penicilinas , Distribución Aleatoria , Ratas Sprague-Dawley , Resveratrol , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND AND PURPOSE: In the treatment of acute thromboembolic stroke, the effectiveness and success of thrombus removal when using stent retrievers is variable. In this study, we analyzed the correlation of thrombectomy maneuver count with a good clinical outcome and recanalization success. MATERIALS AND METHODS: One hundred and four patients with acute occlusion of the middle cerebral artery or the terminal internal carotid artery who were treated with thrombectomy were included in this retrospective study. A good clinical outcome was defined as a 90-day mRS of ≤2, and successful recanalization was defined as TICI 2b-3. RESULTS: The maneuver count ranged between 1-10, with a median of 2. Multivariate logistic regression analyses identified an increasing number of thrombectomy maneuvers as an independent predictor of poor outcome (adjusted OR, 0.59; 95% CI, 0.38-0.87; P = .011) and unsuccessful recanalization (adjusted OR, 0.48; 95% CI, 0.32-0.66; P < .001). A good outcome was significantly more likely if finished within 2 maneuvers compared with 3 or 4 maneuvers, or even more than 4 maneuvers (P < .001). CONCLUSIONS: An increasing maneuver count correlates strongly with a decreasing probability of both good outcome and recanalization. The probability of successful recanalization decreases below 50% if not achieved within 5 thrombectomy maneuvers. Patients who are recanalized within 2 maneuvers have the best chance of achieving a good clinical outcome.
Asunto(s)
Isquemia Encefálica/cirugía , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/cirugía , Isquemia Encefálica/diagnóstico por imagen , Arteria Carótida Interna/cirugía , Estenosis Carotídea/cirugía , Remoción de Dispositivos , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Accidente Cerebrovascular/diagnóstico por imagen , Resultado del TratamientoRESUMEN
PURPOSE: Intra-arterial (IA) administration of nimodipine has been shown to be an effective treatment for subarachnoid hemorrhage-related cerebral vasospasm. The concentrations achieved in cerebral arteries during this procedure, though, are unknown. Therefore, there are no clinical studies investigating dose-dependent effects of nimodipine. We aimed at providing a pharmacokinetic model for IA nimodipine therapy for this purpose. METHODS: A two-compartment pharmacokinetic model for intravenous nimodipine therapy was modified and used to assess cerebral arterial nimodipine concentration during IA nimodipine infusion into the internal carotid artery (ICA). RESULTS: According to our simulations, continuous IA nimodipine infusion at 2 mg/h and 1 mg/h resulted in steady-state cerebral arterial concentrations of about 200 ng/ml and 100 ng/ml assuming an ICA blood flow of 200 ml/min and a clearance of 70 l/h. About 85 % of the maximal concentration is achieved within the first minute of IA infusion independent on the infusion dose. Within the range of physiological and pharmacokinetic data available in the literature, ICA blood flow has more impact on cerebral arterial concentration than nimodipine clearance. CONCLUSION: The presented pharmacokinetic model is suitable for estimations of cerebral arterial nimodipine concentration during IA infusion. It may, for instance, assist in dose-dependent analyses of angiographic results.
Asunto(s)
Modelos Cardiovasculares , Nimodipina/administración & dosificación , Nimodipina/farmacocinética , Hemorragia Subaracnoidea/tratamiento farmacológico , Hemorragia Subaracnoidea/metabolismo , Vasoespasmo Intracraneal/tratamiento farmacológico , Vasoespasmo Intracraneal/metabolismo , Simulación por Computador , Humanos , Inyecciones Intraarteriales , Tasa de Depuración Metabólica , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Hemorragia Subaracnoidea/etiología , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacocinética , Vasoespasmo Intracraneal/complicacionesRESUMEN
The aim of this study was to perform the effects of diabetes on the permeability of the blood-brain barrier (BBB) during pentylenetetrazole (PTZ)-induced epileptic attacks. For this propose, the animals were divided into four groups. These groups contained were intact, PTZ-treated, diabetic and PTZ-treated diabetic individuals, respectively. To evaluate the functioning of the BBB, Evans blue was used as a BBB permeability indicator, and the expressions of zonula occludens-1 and glial fibrillary acidic protein involving the functioning of the BBB were determined immunohistochemically. Also, the changes in the release of serum tumour necrosis factor-alpha and interleukin-10 and interleukin-12 were studied by using enzyme-linked immunosorbent assay method. BBB permeability in the seizures under diabetic conditions showed a considerable increase (p < 0·01) in all of the brain we studied. The immunoreactive staining intensity of zonula occludens-1 and glial fibrillary acidic protein was found reduced in the brain regions of diabetic rats (p < 0·01). However, the serum level of tumour necrosis factor-alpha increased in diabetes and diabetes + PTZ groups, and the serum level of interleukin-12 increased significantly in all experimental groups (p < 0·05). In conclusion, diabetes dramatically increases BBB damage during epileptic seizures, and it may be derived from an elevation of paracellular passage.
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Barrera Hematoencefálica/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Epilepsia/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Animales , Astrocitos/metabolismo , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Barrera Hematoencefálica/química , Convulsivantes/farmacología , Citocinas/sangre , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/fisiopatología , Epilepsia/fisiopatología , Femenino , Pentilenotetrazol/farmacología , Permeabilidad , Ratas Wistar , Estreptozocina , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
Apart from its repressing effect on plasma lipid levels, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors exert neuroprotective functions in animal models of neurodegenerative disorders. In view of these promising observations, we were interested in whether HMG-CoA reductase inhibition would affect epileptiform activity in the brain. To elucidate this issue, atorvastatin, simvastatin and rosuvastatin were administered orally at a dose of 20 mg/kg each for 3 days and their anti-epileptic activities were tested and compared in rats. Epileptiform activity in the brain was induced by an intracortical penicillin G injection. Among HMG-CoA reductase inhibitors, simvastatin-treatment was less effective in terms of spike frequency as compared with atorvastatin- and rosuvastatin-treated animals. Atorvastatin treatment reduced spike frequencies and amplitudes significantly throughout the experiment. However, the most pronounced anti-epileptic effect was observed in rosuvastatin-treated animals, which was associated with improved blood-brain barrier (BBB) integrity, increased expression of endothelial nitric oxide synthase (eNOS) mRNA and decreased expressions of pro-apoptotic p53, Bax and caspase-3 mRNAs. Inhibition of eNOS activity with L-NG-Nitroarginine Methyl Ester (L-NAME) reversed the anti-epileptic effect of rosuvastatin significantly. However, L-NAME did not alter the effect of rosuvastatin on the levels of p53, Bax and caspase-3 mRNA expression. Here, we provide evidence that among HMG-CoA reductase inhibitors, rosuvastatin was the most effective statin on the reduction of epileptiform activity, which was associated with improved BBB permeability, increased expression of eNOS and decreased expressions of pro-apoptotic p53, Bax and caspase-3. Our observation also revealed that the anti-epileptic effect of rosuvastatin was dependent on the increased expression level of eNOS. The robust anti-epileptic effect encourages proof-of-concept studies with rosuvastatin in human epilepsy patients with hypercholesterolemia.
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Encéfalo/efectos de los fármacos , Epilepsia/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Óxido Nítrico Sintasa de Tipo III/metabolismo , Rosuvastatina Cálcica/farmacología , Animales , Anticonvulsivantes/farmacología , Atorvastatina/farmacología , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/fisiopatología , Encéfalo/fisiopatología , Permeabilidad Capilar/efectos de los fármacos , Permeabilidad Capilar/fisiología , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Epilepsia/fisiopatología , Masculino , Óxido Nítrico Sintasa de Tipo III/antagonistas & inhibidores , Penicilina G , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Simvastatina/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
PURPOSE: Assuming thromboembolic events to be the origin of silent strokes during cerebral digital subtraction angiography (DSA), antiplatelet therapy with acetylsalicylic acid (ASA) should significantly reduce the risk for DSA-related silent stroke. The aim of this retrospective analysis was to assess whether ASA does prevent DSA-related silent stroke in terms of high signal intensity lesions in diffusion-weighted magnetic resonance imaging (DW-MRI). METHODS: All patients underwent a baseline DW-MRI 24 h before DSA and a follow-up DW-MRI 3-24 h after DSA. Patients were considered to have an acute (silent) infarction caused by DSA if there was at least one hyperintense lesion of at least 1 mm in diameter and no neurological deficits. RESULTS: Out of 52 patients in the ASA group 11 (21.2%) had high signal lesions on DW-MRI and 20 out of 123 (16.3%) in the non-ASA group. No significant relationship between the ASA and non-ASA group and the post-angiographic appearance of high signal intensity lesions in DW-MRI could be found (Wilcoxon 2-sample test: p-value 0.9). CONCLUSIONS: The use of oral antiplatelet therapy by ASA (100 mg/day) in cerebrovascular patients did not prevent DSA-related high signal intensity lesions in DW-MRI in this study. Despite a potential bias of this retrospective analysis the findings challenge the current theory of thromboembolisms being the predominant origin of silent stroke. The findings therefore support alternative hypotheseses of the etiology of silent strokes, such as air embolism and mobilized embolic material by the catheter at the vessel wall.
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Angiografía de Substracción Digital/efectos adversos , Aspirina/uso terapéutico , Trastornos Cerebrovasculares/diagnóstico , Embolia Intracraneal , Trastornos Cerebrovasculares/complicaciones , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Embolia Intracraneal/diagnóstico , Embolia Intracraneal/etiología , Embolia Intracraneal/prevención & control , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
The aim of this study was to compare the effects of hypoglycemia and induced convulsions on the blood-brain barrier permeability in rats with or without lifelong administration of sodium selenite. There is a significant decrease of the blood-brain barrier permeability in three brain regions of convulsive, hypoglycemic male rats treated with sodium selenite when compared to sex-matched untreated rats (p<0.05), but the decrease was not significant in female rats (p>0.05). The blood-brain barrier permeability of the left and right hemispheres of untreated, moderately hypoglycemic convulsive rats of both genders was better than their untreated counterparts (p<0.05). Our results suggest that moderate hypoglycemia and lifelong treatment with sodium selenite have a protective effect against blood-brain barrier permeability during convulsions and that the effects of sodium selenite are gender-dependent.
Asunto(s)
Barrera Hematoencefálica/metabolismo , Hipoglucemia/metabolismo , Convulsiones/metabolismo , Caracteres Sexuales , Selenito de Sodio/administración & dosificación , Selenito de Sodio/farmacología , Animales , Presión Sanguínea , Femenino , Masculino , Ratas , Ratas Wistar , Selenito de Sodio/metabolismo , Factores de TiempoRESUMEN
Our purpose in this study was to investigate the protective effects of selenium and vitamin E on the blood-brain barrier (BBB) permeability in rats with convulsion under hyperthermic conditions. To eliminate the effect of sex on BBB, we performed our study on 4- to 5-week-old prepubertal rat pups. Evans-blue was used as a BBB tracer. Convulsions were induced by administration of i.p. pentylenetetrazol. In the selenium group, 4 ppm selenium was added to the drinking water for 4-5 weeks. Vitamin E was administered at 700 mg/kg ip. It was shown that the convulsions, both under normothermic and hyperthermic conditions, caused widespread increase in the BBB permeability (p < 0.05). In addition, a significant difference was observed among female and male rats (f [1, 102] = 6.387, p < 0.05). In convulsions under normothermic conditions, there was a further increase in the BBB permeability (F[3, 102] = 43.534, p < 0.001) and a greater increase of permeability in males compared to females (F[1, 102] = 6.387, p < 0.05). Selenium and vitamin E significantly decreased the BBB destruction caused by convulsions under hyperthermic conditions in males (p < 0.05). Treatment with selenium or vitamin E has beneficial effects on the BBB breakdown during convulsions. But gender differences are very important in BBB permeability under pathological conditions and antioxidant treatments.