RESUMEN
Let-7i modulates the physical function and inflammation in endothelial cells (ECs). However, whether the let-7i of ECs involves in brain vasculature and ischemic stroke is unknown. Using inducible Cadherin5-Cre lineage-tracking mice, a loxp-RNA-sponge conditional knockdown of let-7 in ECs- induced increase of transforming growth factor-ß receptor type 1 (TGF-ßR1), endothelial-mesenchymal transition (endMT), vascular fibrosis, and opening of the brain-blood barrier (BBB). By this lineage-tracking mice, we found that ECs underwent endMT after transient middle cerebral artery occlusion (MCAO). Through specifically overexpressed let-7i in ECs, we found that it reduced TGF-ßR1, endMT, and vascular fibrosis. Furthermore, this overexpression reduced the infarct volume and leakage of the BBB, and improved the neurological function. Further, the expression of let-7i decreased after MCAO, but was reversed by antagonist of TGF-ßR1 or inhibition of Mek phosphorylation. And the inhibition of Mek attenuated the vascular fibrosis after MCAO. In summary, we concluded that ischemic stroke activates a let-7i/TGF-ßR1 double-negative feedback loop, thereby inducing endMT and vascular fibrosis. These results suggest that endMT is a potential target for the treatment of cerebral vascular fibrosis.
Asunto(s)
Traumatismos Cerebrovasculares/patología , Traumatismos Cerebrovasculares/fisiopatología , MicroARNs/genética , MicroARNs/fisiología , Receptor Tipo I de Factor de Crecimiento Transformador beta/genética , Receptor Tipo I de Factor de Crecimiento Transformador beta/fisiología , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Animales , Barrera Hematoencefálica/patología , Barrera Hematoencefálica/fisiopatología , Transdiferenciación Celular , Modelos Animales de Enfermedad , Endotelio/patología , Endotelio/fisiopatología , Retroalimentación Fisiológica , Fibrosis , Técnicas de Silenciamiento del Gen , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/fisiopatología , Masculino , Mesodermo/patología , Mesodermo/fisiopatología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Ratas , Ratas Sprague-Dawley , Receptor Tipo I de Factor de Crecimiento Transformador beta/deficienciaRESUMEN
Dysfunction of the cerebrovasculature plays an important role in vascular cognitive impairment (VCI). Lipotoxic injury of the systemic endothelium in response to hydrolyzed triglyceride-rich lipoproteins (TGRLs; TGRL lipolysis products) or a high-fat Western diet (WD) suggests similar mechanisms may be present in brain microvascular endothelium. We investigated the hypothesis that TGRL lipolysis products cause lipotoxic injury to brain microvascular endothelium by generating increased mitochondrial superoxide radical generation, upregulation of activating transcription factor 3 (ATF3)-dependent inflammatory pathways, and activation of cellular oxidative stress and apoptotic pathways. Human brain microvascular endothelial cells were treated with human TGRL lipolysis products that induced intracellular lipid droplet formation, mitochondrial superoxide generation, ATF3-dependent transcription of proinflammatory, stress response, and oxidative stress genes, as well as activation of proapoptotic cascades. Male apoE knockout mice were fed a high-fat/high-cholesterol WD for 2 months, and brain microvessels were isolated by laser capture microdissection. ATF3 gene transcription was elevated 8-fold in the hippocampus and cerebellar brain region of the WD-fed animals compared with chow-fed control animals. The microvascular injury phenotypes observed in vitro and in vivo were similar. ATF3 plays an important role in mediating brain microvascular responses to acute and chronic lipotoxic injury and may be an important preventative and therapeutic target for endothelial dysfunction in VCI.
Asunto(s)
Factor de Transcripción Activador 3/genética , Traumatismos Cerebrovasculares/genética , Disfunción Cognitiva/genética , Inflamación/genética , Lipoproteínas/metabolismo , Triglicéridos/metabolismo , Factor de Transcripción Activador 3/biosíntesis , Animales , Cerebelo/irrigación sanguínea , Cerebelo/metabolismo , Cerebelo/patología , Traumatismos Cerebrovasculares/metabolismo , Traumatismos Cerebrovasculares/fisiopatología , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Dieta Alta en Grasa/efectos adversos , Dieta Occidental/efectos adversos , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Hipocampo/irrigación sanguínea , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Inflamación/metabolismo , Inflamación/fisiopatología , Ratones , Estrés Oxidativo/genética , Transducción de Señal/genéticaRESUMEN
Aneurysmal subarachnoid hemorrhage is a serious medical and social problem. The main physiological mechanisms that determine secondary brain damage in this patients are intracranial hypertension, cerebral vasospasm, dysfunction of autoregulation mechanisms, violation of liquorodynamics and delayed cerebral ischemia. The multimodal neuromonitoring for prevention and timely correction ofsecondary brain injury factors has become routine practice in neuroICU. Measurement of oxygen tension in the brain parenchyma is one of neuromonitoring options. During the years of intensive use of this method in clinical practice the reasons for reducing the oxygen tension in the brain parenchyma were revealed, as well as developed and clinically validated algorithms for correction of such conditions. However, there are clinical situations that are difficult to interpret and even more difficult to make the right tactical and therapeutic solutions. We present the clinical observation of the patient with aneurysmal subarachnoid hemorrhage, who had dramatically reduced brain intraparenchymal oxygen pressure although prolonged hypothermia were used. Despite this, the outcome was favorable. The analysis allowed to assume that the reason for this decrease in oxygen tension in the brain parenchyma could be hypothermia itself
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Isquemia Encefálica/fisiopatología , Traumatismos Cerebrovasculares/fisiopatología , Hipertensión Intracraneal/fisiopatología , Oxígeno/metabolismo , Hemorragia Subaracnoidea/fisiopatología , Análisis de los Gases de la Sangre , Encéfalo/metabolismo , Encéfalo/fisiopatología , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Circulación Cerebrovascular , Traumatismos Cerebrovasculares/diagnóstico por imagen , Traumatismos Cerebrovasculares/terapia , Femenino , Humanos , Hipotermia Inducida/métodos , Hipertensión Intracraneal/diagnóstico por imagen , Hipertensión Intracraneal/terapia , Presión Intracraneal/fisiología , Persona de Mediana Edad , Monitoreo Fisiológico , Tejido Parenquimatoso/metabolismo , Tejido Parenquimatoso/fisiopatología , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/cirugía , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND AND PURPOSE: Emerging evidence suggests that atrial disease is associated with vascular brain injury in the absence of atrial fibrillation. METHODS: The Cardiovascular Health Study prospectively enrolled community-dwelling adults aged ≥65 years. Among participants who underwent MRI, we examined associations of ECG left atrial abnormality with brain infarcts and leukoaraiosis. P-wave terminal force in lead V1 was the primary measure of left atrial abnormality; P-wave area and duration were secondary predictors. We excluded participants with atrial fibrillation before or on their index ECG. Primary outcomes were incident infarcts and worsening leukoaraiosis from initial to follow-up scan ≈5 years later. Secondary outcomes were prevalent infarcts and degree of leukoaraiosis on initial MRI. Relative risk (RR) and linear regression models were adjusted for vascular risk factors. RESULTS: Among 3129 participants with ≥1 scan, each SD increase in P-wave terminal force in lead V1 was associated with a 0.05-point (95% confidence interval [CI], 0.0003-0.10) higher baseline white matter grade on a 10-point scale. P-wave terminal force in lead V1 was associated with prevalent infarcts of any type (RR per SD, 1.09; 95% CI, 1.04-1.16) and more so with prevalent nonlacunar infarcts (RR per SD, 1.22; 95% CI, 1.08-1.38). Among 1839 participants with 2 scans, P-wave terminal force in lead V1 was associated with worsening leukoaraiosis (RR per SD, 1.09; 95% CI, 1.01-1.18), but not with incident infarcts (RR per SD, 1.06; 95% CI, 0.93-1.20). Sensitivity analyses adjusting for incident atrial fibrillation found similar results. P-wave area and duration were not associated with outcomes. CONCLUSIONS: ECG left atrial abnormality is associated with vascular brain injury in the absence of documented atrial fibrillation.
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Traumatismos Cerebrovasculares/fisiopatología , Electrocardiografía , Atrios Cardíacos/fisiopatología , Imagen por Resonancia Magnética , Anciano , Fibrilación Atrial , Encéfalo/fisiopatología , Infarto Encefálico , Enfermedades Cardiovasculares/fisiopatología , Traumatismos Cerebrovasculares/complicaciones , Femenino , Atrios Cardíacos/diagnóstico por imagen , Cardiopatías/complicaciones , Cardiopatías/diagnóstico por imagen , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Resultado del Tratamiento , UltrasonografíaAsunto(s)
Isquemia Encefálica , Traumatismos Cerebrovasculares , Accidente Cerebrovascular , Animales , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/terapia , Traumatismos Cerebrovasculares/complicaciones , Traumatismos Cerebrovasculares/patología , Traumatismos Cerebrovasculares/fisiopatología , Traumatismos Cerebrovasculares/terapia , Humanos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapiaRESUMEN
OBJECTIVE: To investigate whether microvascular damage is involved in the pathogenesis of heroin induced spongiform leukoencephalopathy (HSLE). METHODS: The brain tissues were collected from 4 HSLE patients and 5 controls and then fixed in 4% paraformaldehyde. The frontal lobe, corpus callosum and cerebellum were separated. The expressions of myelin base protein (MBP) and CD34 were detected by immunohistochemistry. TUNEL staining was applied to detect cell apoptosis. The correlation between microvascular changes and pathological vacuoles was evaluated. RESULTS: No obvious abnormalities were found in the brain of controls. Immunohistochemistry for MBP showed the collapse and fracture of myelin sheath and vacuole formation in the subcortical white matter, corpus callosum, and cerebellar white matter of HSLE patients. TUNEL staining showed the number of apoptotic cells in the cerebellar white matter and corpus callosum of HSLE patients was significantly higher than that in controls (F = 389.451, P < 0.001). Masson's trichrome staining revealed vacuolar degeneration in the cerebral white matter of HSLE patients, and the vacuoles were distributed around the microvessels. Immunohistochemistry revealed CD34 positive cells were seldom found besides the vessels in the cerebellar white matter and corpus callosum of HSLE patients, but a variety of CD34 positive cells was found in the vascular wall of controls (F = 838.500, P < 0.001). CONCLUSION: Apoptosis of oligodendrocytes may be related to the HSLE. Cerebral vascular injury and microcirculation dysfunction are involved in the pathogenesis of HSLE. The interrelation between apoptosis of oligodendrocytes and the microvascular damage are required to be studied in future investigations.
Asunto(s)
Antígenos CD34/metabolismo , Enfermedad de Canavan/fisiopatología , Traumatismos Cerebrovasculares/fisiopatología , Dependencia de Heroína/fisiopatología , Microvasos/patología , Proteína Básica de Mielina/metabolismo , Adulto , Apoptosis , Enfermedad de Canavan/inducido químicamente , Enfermedad de Canavan/metabolismo , Cerebelo/irrigación sanguínea , Cerebelo/metabolismo , Cerebelo/patología , Traumatismos Cerebrovasculares/metabolismo , Cuerpo Calloso/irrigación sanguínea , Cuerpo Calloso/metabolismo , Cuerpo Calloso/patología , Femenino , Lóbulo Frontal/irrigación sanguínea , Lóbulo Frontal/metabolismo , Lóbulo Frontal/patología , Heroína/toxicidad , Dependencia de Heroína/metabolismo , Humanos , Masculino , Microvasos/metabolismo , Persona de Mediana Edad , Oligodendroglía/metabolismo , Oligodendroglía/patologíaRESUMEN
BACKGROUND: Emerging evidence shows sex differences in manifestations of vascular brain injury in memory clinic patients. We hypothesize that this is explained by sex differences in cardiovascular function. OBJECTIVE: To assess the relation between sex and manifestations of vascular brain injury in patients with cognitive complaints, in interaction with cardiovascular function. METHODS: 160 outpatient clinic patients (68.8±8.5 years, 38% female) with cognitive complaints and vascular brain injury from the Heart-Brain Connection study underwent a standardized work-up, including heart-brain MRI. We calculated sex differences in vascular brain injury (lacunar infarcts, non-lacunar infarcts, white matter hyperintensities [WMHs], and microbleeds) and cardiovascular function (arterial stiffness, cardiac index, left ventricular [LV] mass index, LV mass-to-volume ratio and cerebral blood flow). In separate regression models, we analyzed the interaction effect between sex and cardiovascular function markers on manifestations of vascular brain injury with interaction terms (sex*cardiovascular function marker). RESULTS: Males had more infarcts, whereas females tended to have larger WMH-volumes. Males had higher LV mass indexes and LV mass-to-volume ratios and lower CBF values compared to females. Yet, we found no interaction effect between sex and individual cardiovascular function markers in relation to the different manifestations of vascular brain injury (p-values interaction termsâ>â0.05). CONCLUSION: Manifestations of vascular brain injury in patients with cognitive complaints differed by sex. There was no interaction between sex and cardiovascular function, warranting further studies to explain the observed sex differences in injury patterns.
Asunto(s)
Traumatismos Cerebrovasculares/fisiopatología , Disfunción Cognitiva/fisiopatología , Hipertensión/fisiopatología , Sustancia Blanca/patología , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Factores Sexuales , Accidente Vascular Cerebral Lacunar/fisiopatologíaRESUMEN
STUDY DESIGN: Retrospective clinical series. OBJECTIVE: To evaluate the management and outcomes of patients with unilateral, asymptomatic vertebral artery occlusion (VAO) undergoing surgery for cervical fractures associated with subluxation. SUMMARY OF BACKGROUND DATA: The management of VAO is controversial with several treatment options available, including observation alone, antiplatelet therapy, or anticoagulation therapy. METHODS: A chart review inclusive of the years 2004 to 2006 was performed to include patients who presented after nonpenetrating trauma with cervical fracture associated with subluxation requiring surgery. An associated asymptomatic VAO was also required for inclusion. Eight patients were identified. RESULTS: Seven patients were male and the mean age was 26.8 years. Six patients suffered an associated spinal cord injury. Three patients underwent closed reduction before surgical stabilization. Five patients underwent open reduction with stabilization. No patient received treatment for VAO before reduction. Postoperative treatment for VAO was variable, with 5 of 8 patients undergoing observation alone. The remaining 3 patients were treated with aspirin therapy, although 1 patient received heparin intravenously for 1 day. None of the patients experienced an ischemic complication. CONCLUSIONS: Reduction of a fracture, whether closed or open, without treatment of an associated asymptomatic VAO seems safe. Postoperative management of VAO consisting of either observation alone or aspirin therapy also seems to be a safe option.
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Traumatismos Cerebrovasculares/cirugía , Vértebras Cervicales/lesiones , Vértebras Cervicales/cirugía , Fracturas de la Columna Vertebral/cirugía , Arteria Vertebral/lesiones , Arteria Vertebral/cirugía , Adolescente , Adulto , Traumatismos Cerebrovasculares/etiología , Traumatismos Cerebrovasculares/fisiopatología , Vértebras Cervicales/patología , Estudios de Cohortes , Femenino , Humanos , Fijadores Internos , Luxaciones Articulares/complicaciones , Luxaciones Articulares/patología , Luxaciones Articulares/cirugía , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Cuidados Posoperatorios , Estudios Retrospectivos , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/fisiopatología , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/patología , Fusión Vertebral/instrumentación , Fusión Vertebral/métodos , Resultado del Tratamiento , Arteria Vertebral/patología , Disección de la Arteria Vertebral/etiología , Disección de la Arteria Vertebral/fisiopatología , Disección de la Arteria Vertebral/cirugía , Adulto JovenRESUMEN
BACKGROUND: Current blunt cerebrovascular injury (BCVI) grading grossly differentiates injury characteristics such as luminal stenosis (LS) and aneurysmal disease. The effect of increasing degree of LS beyond the current BCVI grading scale on stroke formation is unknown. STUDY DESIGN: BCVI over a 3-year period were retrospectively reviewed. To investigate influence of LS beyond the BCVI grading scale within aneurysmal and non-aneurysmal BCVI, grade 2 BCVI were subdivided into BCVI with ≥ 25% and ≤ 50% LS and BCVI with > 50% and ≤ 99% LS. Grade 3 BCVI were subdivided into BCVI with pseudoaneurysm (PSA) without LS and BCVI with PSA and LS. We hypothesized increased LS beyond the current BCVI grade distinctions would be associated with higher rates of stroke formation. RESULTS: 312 BCVI were included, of which 140 were carotid BCVI and 172 vertebral BCVI. Sixteen carotid BCVI underwent endovascular intervention (EI) and 19 suffered a stroke. In carotid BCVI stroke rates increased sequentially with BCVI grade except in grade 3. There was a stroke rate of 12% in grade 1 carotid BCVI, 18% in grade 2, 6% in grade 3, and 31% in grade 4. In subgroup analysis for grade 2 carotid BCVI, BCVI with > 50% and ≤ 99% LS had higher rates of stroke (22% vs. 15%, p = 0.44) than BCVI with ≥ 25% and ≤ 50% LS. In subgroup analysis of grade 3 carotid BCVI, BCVI with PSA and LS had higher rates of stroke (9% vs. 4%, p = 0.48) than BCVI with PSA without LS. Higher rates of EI in grade 2 carotid BCVI with > 50% and ≤ 99% LS (22% vs. 5%, p = 0.14) and grade 3 carotid BCVI with PSA and LS (35% vs. 4%, p = 0.01) were noted in subgroup analysis. CONCLUSION: Higher percentage LS beyond the currently used BCVI grading scale has a non-significantly increased rate of stroke in both aneurysmal and non-aneurysmal BCVI. Grade 3 BCVI with PSA and LS seems to be a high-risk subgroup. Use of EI confounds modern measurement of stroke risk in higher LS BCVI.
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Traumatismos de las Arterias Carótidas/fisiopatología , Traumatismos Cerebrovasculares/complicaciones , Constricción Patológica/fisiopatología , Accidente Cerebrovascular/etiología , Heridas no Penetrantes/complicaciones , Adulto , Angiografía Cerebral , Traumatismos Cerebrovasculares/fisiopatología , Traumatismos Cerebrovasculares/terapia , Embolización Terapéutica/métodos , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Accidente Cerebrovascular/fisiopatología , Heridas no Penetrantes/fisiopatología , Heridas no Penetrantes/terapia , Adulto JovenRESUMEN
Since blunt cerebrovascular injury (BCVI) became increasingly recognized more than 20 years ago, significant improvements have been made in both diagnosis and treatment. Little is known regarding long-term functional outcomes in BCVI. The purpose of this study was to evaluate the impact of BCVI on those long-term outcomes. All patients with BCVI from 1996 to 2014 were identified from the trauma registry. Functional outcome was measured using the Boston University Activity Measure for Post-Acute Care. Multiple regression analysis was performed to identify potential predictors of outcomes. A total of 509 patients were identified. Overall mortality was 18 per cent (BCVI-related = 1%). Of the 415 survivors, follow-up was obtained in 77 (19%). Mean follow-up was five years, with a maximum of 19 years. Mean age and injury severity score were 47 and 25, respectively. Six (8%) patients suffered strokes. Mean Activity Measure for Post-Acute Care scores were 59 (mobility), 58 (activity), and 44 (cognitive function), each indicating significant impairment compared with normal. Multiple regression models identified 1) age as a predictor of decreased mobility, 2) injury severity score as a predictor of decreased mobility, activity, and cognitive function, and 3) stroke as a predictor of decreased activity, cognitive function, and likely mobility. Development of stroke and increased injury severity resulted in worse long-term functional outcomes after BCVI. Thus, stroke prevention with optimal diagnostic and treatment algorithms remains critical in the successful treatment of BCVI because it has significant impact on long-term functional outcomes and is the only modifiable predictor of outcomes in patients after BCVI.
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Traumatismos Cerebrovasculares/fisiopatología , Heridas no Penetrantes/fisiopatología , Actividades Cotidianas , Adulto , Anciano , Traumatismos Cerebrovasculares/complicaciones , Traumatismos Cerebrovasculares/diagnóstico , Traumatismos Cerebrovasculares/mortalidad , Cognición , Femenino , Estudios de Seguimiento , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Limitación de la Movilidad , Pronóstico , Sistema de Registros , Análisis de Regresión , Accidente Cerebrovascular/etiología , Tennessee/epidemiología , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/mortalidadRESUMEN
INTRODUCTION: Practice management guidelines for screening and treatment of patients with blunt cerebrovascular injury (BCVI) have been associated with a decreased risk of ischemic stroke. TREATMENT: of patients with BCVI and multisystem injuries that delays immediate antithrombotic therapy remains controversial. The purpose of this study was to determine the timing of BCVI treatment initiation, the incidence of stroke, and bleeding complications as a result of antithrombotic therapy in patients with isolated BCVI in comparison to those with BCVI complicated by multisystem injuries. MATERIALS AND METHODS: This study was a retrospective review of all adult blunt trauma patients admitted to a level 1 trauma center from 2009 to 2014 with a diagnosis of BCVI. RESULTS: A total of 28,305 blunt trauma patients were admitted during the study period. Of these, 323 (1.1%) had 481 BCEVIs and were separated into two groups. Isolated BCVI was reported in 111 (34.4%) patients and 212 (65.6%) patients had accompanying multisystem injuries (traumatic brain injury (TBI), solid organ injury, or spinal cord injury) that contraindicated immediate antithrombotic therapy. TREATMENT: started in patients with isolated BCVI at a median time of 30.3 (15, 52) hours after injury in contrast to 62.4 (38, 97) hours for those with multisystem injuries (p<0.001). The incidence of stroke was identical (9.9%) between groups and no bleeding complications related to antithrombotic therapy were identified. CONCLUSION: The lack of bleeding complications and equivalent stroke rates between groups suggests that the presence of TBI, solid organ injury, and spinal cord injury are not contraindications to anti-thrombotic therapy for stroke prevention in patients with BCVI.
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Traumatismos Cerebrovasculares/tratamiento farmacológico , Fibrinolíticos/efectos adversos , Traumatismo Múltiple/terapia , Accidente Cerebrovascular/prevención & control , Heridas no Penetrantes/tratamiento farmacológico , Adulto , Traumatismos Cerebrovasculares/fisiopatología , Contraindicaciones , Esquema de Medicación , Femenino , Fibrinolíticos/uso terapéutico , Guías como Asunto , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/fisiopatología , Estudios Retrospectivos , Prevención Secundaria , Accidente Cerebrovascular/inducido químicamente , Factores de Tiempo , Tomografía Computarizada por Rayos X , Centros Traumatológicos , Resultado del Tratamiento , Heridas no Penetrantes/fisiopatologíaRESUMEN
HYPOTHESIS: We hypothesized that P wave terminal Force in the V1 lead (PTFV1) would be associated with leukoaraiosis and subclinical infarcts, especially cortical infarcts, in a population-based, multi-ethnic cohort. METHODS: PTFV1 was collected manually from baseline electrocardiograms of clinically stroke-free Northern Manhattan Study participants. Investigators read brain MRIs for superficial infarcts, deep infarcts, and white matter hyperintensity volume (WMHV). WMHV was adjusted for head size and log transformed, achieving a normal distribution. Logistic regression models investigated the association of PTFV1 with cortical and with all subclinical infarcts. Linear regression models examined logWMHV. Models were adjusted for demographics and risk factors. RESULTS: Among 1174 participants with PTFV1 measurements, the mean age at MRI was 70 ± 9 years. Participants were 14.4% white, 17.6% black, and 65.8% Hispanic. Mean PTFV1 was 3587.35 ± 2315.62 µV-ms. Of the 170 subclinical infarcts, 40 were cortical. PTFV1 ≥ 5000 µV-ms was associated with WMHV in a fully adjusted model (mean difference in logWMHV 0.15, 95% confidence interval 0.01-0.28). PTFV1 exhibited a trend toward an association with cortical infarcts (unadjusted OR per SD change logPTFV1 1.30, 95% CI 0.94-1.81), but not with all subclinical infarcts. CONCLUSION: Electrocardiographic evidence of left atrial abnormality was associated with leukoaraiosis.
Asunto(s)
Arritmias Cardíacas/diagnóstico , Traumatismos Cerebrovasculares/diagnóstico por imagen , Atrios Cardíacos/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico , Anciano , Anciano de 80 o más Años , Arritmias Cardíacas/diagnóstico por imagen , Arritmias Cardíacas/fisiopatología , Presión Sanguínea , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/fisiopatología , Traumatismos Cerebrovasculares/fisiopatología , Electrocardiografía , Femenino , Atrios Cardíacos/fisiopatología , Humanos , Hipertensión/diagnóstico , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Leucoaraiosis/diagnóstico , Leucoaraiosis/diagnóstico por imagen , Leucoaraiosis/fisiopatología , Leucoencefalopatías/diagnóstico , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/fisiopatología , Imagen por Resonancia Magnética , Masculino , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND: Blunt cerebrovascular injury is uncommon in the pediatric population; penetrating cerebrovascular injuries are even rarer and are thus poorly understood. OBJECTIVE: To describe the diagnosis and management of penetrating cerebrovascular injuries and describe outcomes of available treatment modalities. METHODS: Clinical and radiographic data were collected retrospectively from a multicenter trauma registry for children screened for cerebrovascular injury during 2003 to 2013 at 4 academic pediatric trauma centers. RESULTS: Among 645 pediatric patients evaluated with computed tomography angiography with blunt cerebrovascular injury, 130 also had a penetrating trauma indication. Seven penetrating cerebrovascular injuries were diagnosed in 7 male patients (mean age 12.4 years, range 12-18 years). Focal neurological deficit and concomitant intracranial injury were each seen in 2 patients. There were 2 intracranial carotid artery injuries, 4 extracranial carotid artery injuries, and 1 vertebral artery injury. The majority of injuries were higher than grade I (5/7; 71%): 2 were grade I, 1 grade II, 2 grade III, and 2 grade IV. The 2 patients with grade III injuries required open surgery, and 1 patient with a grade IV injury underwent endovascular treatment. Two patients suffered immediate stroke secondary to the penetrating cerebrovascular injury. There were no delayed neurological deficits from the penetrating injuries, and no patients died as a result of the injuries. CONCLUSION: This is the largest series of penetrating cerebrovascular trauma in the pediatric literature. Although rare, penetrating cerebrovascular injuries can be high-grade injuries that require urgent recognition and may require aggressive endovascular and/or open surgery for treatment.
Asunto(s)
Traumatismos Cerebrovasculares , Heridas Penetrantes , Adolescente , Traumatismos Cerebrovasculares/diagnóstico , Traumatismos Cerebrovasculares/epidemiología , Traumatismos Cerebrovasculares/fisiopatología , Traumatismos Cerebrovasculares/cirugía , Niño , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Heridas Penetrantes/diagnóstico , Heridas Penetrantes/epidemiología , Heridas Penetrantes/fisiopatología , Heridas Penetrantes/cirugíaRESUMEN
BACKGROUND: The short-term natural history of blunt cerebrovascular injuries (BCVIs) has been previously described in the literature, but the purpose of this study was to analyze long-term serial follow-up and lesion progression of BCVI. METHODS: This is a single institution's retrospective review of a prospectively collected database over four years (2009-2013). All patients with a diagnosis of BCVI by computed tomographic (CT) scan were identified, and injuries were graded based on modified Denver scale. Management followed institutional algorithm: initial whole-body contrast-enhanced CT scan, followed by CT angiography at 24 to 72 hours, 5 to 7 days, 4 to 6 weeks, and 3 months after injury. All follow-up imaging, medication management, and clinical outcomes through 6 months following injury were recorded. RESULTS: There were 379 patients with 509 injuries identified. Three hundred eighty-one injuries were diagnosed as BCVI on first CT (Grade 1 injuries, 126; Grade 2 injuries, 116; Grade 3 injuries, 69; and Grade 4 injuries, 70); 100 "indeterminate" on whole-body CT; 28 injuries were found in patients reimaged only for lesions detected in other vessels. Sixty percent were male, mean (SD) age was 46.5 (19.9) years, 65% were white, and 62% were victims of a motor vehicle crash. Most frequently, Grade 1 injuries were resolved at all subsequent time points. Up to 30% of Grade 2 injuries worsened, but nearly 50% improved or resolved. Forty-six percent of injuries originally not detected were subsequently diagnosed as Grade 3 injuries. Greater than 70% of all imaged Grade 3 and Grade 4 injuries remained unchanged at all subsequent time points. CONCLUSIONS: This study revealed that there are many changes in grade throughout the six-month time period, especially the lesions that start out undetectable or indeterminate, which become various grade injuries. Low-grade injuries (Grades 1 and 2) are likely to remain stable and eventually resolve. Higher-grade injuries (Grades 3 and 4) persist, many up to six months. Inpatient treatment with antiplatelet or anticoagulation did not affect BCVI progression. LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.
Asunto(s)
Traumatismos Cerebrovasculares/patología , Traumatismos Cerebrovasculares/fisiopatología , Heridas no Penetrantes/patología , Heridas no Penetrantes/fisiopatología , Adulto , Anciano , Traumatismos Cerebrovasculares/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Cicatrización de Heridas , Heridas no Penetrantes/terapiaRESUMEN
Perinatal hypoxia is a critical complication during delivery and is mostly studied in animal models of postnatal hypoxic-ischemic brain injury. We here studied the effects of postnatal hypoxic-ischemic brain injury in two different sub-strains of C57BL/6 mice, i.e. C57BL/6J and C57BL/6N mice. These two sub-strains show different metabolic properties, for instance an impaired glucose tolerance in C57BL/6J mice. Genetically, this was linked to differences in their nicotinamide nucleotide transhydrogenase (Nnt) genes: In C57BL/6J mice, exons 7-11 of the Nnt gene are deleted, resulting in the absence of functional Nnt protein. The mitochondrial Nnt-protein is one of several enzymes that catalyses the generation of NADPH, which in turn is important for the elimination of reactive oxygen species (ROS). As ROS is thought to contribute to the pathophysiology of hypoxia-ischemia, the lack of Nnt might indirectly increase ROS levels and therefore result in increased brain damage. We therefore hypothesize that lesion score and lesion size will increase in C57BL/6J mice as compared to C57BL/6N mice. Surprisingly, the results showed exactly the opposite: C57BL/6J mice showed a decrease in lesion score and size, associated with a reduced number of apoptotic cells and activated microglia. In contrast, the number of cells with ROS-induced DNA modifications (detected by 8OHdG) was higher in C57BL/6J than C57BL/6N mice. In conclusion, C57BL/6J mice showed reduced ischemic consequences after postnatal hypoxic-ischemic brain injury compared to C57BL/6N mice, with the exception of the amount of ROS-induced DNA-damage. These differences might relate to the lack of Nnt, but also to a modified metabolic setting (cardiovascular parameters, oxygen and glucose metabolism, immune function) in C57BL/6J mice.
Asunto(s)
Hipoxia-Isquemia Encefálica/fisiopatología , Ratones Endogámicos/metabolismo , Animales , Encéfalo/metabolismo , Lesiones Encefálicas/fisiopatología , Traumatismos Cerebrovasculares/fisiopatología , Exones , Intolerancia a la Glucosa/patología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos/genética , NADP/genética , NADP/metabolismo , NADP Transhidrogenasas/genética , NADP Transhidrogenasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Cognitive functions display a progressive impairment with ageing, and this is thought to be due to the accumulation of neuronal loss or acute and/or repeated microvascular accidents. Chronic damage to the brain cortex lead to decreasing ability of elderly subjects to cope with daily events and ultimately result in loss of self-sufficiency. Since proinflammatory cytokines have been implicated both in cerebrovascular injury due to atherosclerosis and in Alzheimer's disease (AD), we investigated 70 elderly subjects with neurocognitive and functional impairment. Diagnosis was established in 54, the others were included in the "mixed" group. Sera were collected and stored at -70 degrees C until measurement of IL-1beta and TNF-alpha, performed by commercial ELISA kits. Data obtained were analysed with respect to other socio-demographic, psychoneurological and clinical variables. The results show that serum TNF-alpha was lower in mild-moderate AD compared to severe AD and dementias due to vascular disease, as well as the TNF-alpha/IL-1beta ratio. Both cytokines showed a significant relationship with age. Our study suggests that proinflammatory cytokines serum profiles seem to discriminate between mild-moderate AD and vascular or mixed forms of dementia. Furthermore, it offers new evidence of a strong implication of inflammatory mechanisms in atherosclerosis, more than in less severe AD.
Asunto(s)
Enfermedad de Alzheimer/sangre , Demencia Vascular/sangre , Interleucina-1/sangre , Factor de Necrosis Tumoral alfa/análisis , Anciano , Enfermedad de Alzheimer/inmunología , Enfermedad de Alzheimer/fisiopatología , Traumatismos Cerebrovasculares/sangre , Traumatismos Cerebrovasculares/inmunología , Traumatismos Cerebrovasculares/fisiopatología , Estudios Transversales , Demencia Vascular/inmunología , Demencia Vascular/fisiopatología , Femenino , Humanos , Masculino , Análisis MultivarianteRESUMEN
It is recognized that surgical obliteration of the cerebral veins by additional brain compression using retractors is dangerous. However, there is a lack of satisfactory management of this problem. We investigated whether intermittent brain compression can reduce brain injury from cerebral venous circulation disturbances (CVCDs). In Wistar rats (n = 25), a solitary cortical vein was occluded photochemically. The brain surface was compressed by a spring balance and constant compression at 30 mmHg was carried out for 60 min. Intermittent procedure compression protocols included four 15 min compressions at 5 min intervals, intermittent isometric exposure (IM), and intermittent isotonic exposure (IT). Local cerebral blood flow (ICBF) in the compressed area was measured together by laser-Doppler (LD) with the degree of brain compression. After 24 h, the brains were examined histologically. The animals were divided into the following five groups (each n = 5): 1, a sham operated control; 2, cortical vein occlusion (VO); 3, VO + continuous brain compression (CC); 4, VO + IM; and 5, VO + IT. The ICBF decreased significantly during the compression; however, recovery after the series of compressions was observed only in the VO + IM group, not in the VO + CC and the VO + IT groups (p < 0.05). The depth of the brain surface increased stepwise in the VO + IT group compared with the VO + IM group (p < 0.01). The resulting tissue damage was significantly larger in the VO + CC and VO + IT groups than in the vein occlusion group (p < 0.05), but not in the VO + IM group. The results of the present study suggest that intermittent isometric exposure under CVCDs could decrease brain retraction injury during neurosurgical operations and be more beneficial than continuous compression, providing that the compression pressure declines as the process advances.
Asunto(s)
Lesiones Encefálicas/prevención & control , Venas Cerebrales/lesiones , Traumatismos Cerebrovasculares/prevención & control , Complicaciones Intraoperatorias/prevención & control , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/métodos , Presión/efectos adversos , Animales , Fenómenos Biomecánicos , Lesiones Encefálicas/etiología , Lesiones Encefálicas/fisiopatología , Venas Cerebrales/patología , Venas Cerebrales/fisiopatología , Circulación Cerebrovascular/fisiología , Trastornos Cerebrovasculares/complicaciones , Trastornos Cerebrovasculares/fisiopatología , Traumatismos Cerebrovasculares/etiología , Traumatismos Cerebrovasculares/fisiopatología , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/fisiopatología , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
BACKGROUND: There has been much debate on whom to screen, how to screen, and how to treat blunt cerebrovascular injury (BCVI), but there has been little published on long-term functional outcomes following diagnosis and treatment of BCVI. This study was conducted to address those long-term outcomes. METHODS: Patients with BCVI during a 53-month period ending June 2009 were identified. Charts were reviewed for demographics, associated injuries, treatments, strokes, and in-hospital mortality. Posthospital discharge follow-up was conducted. A structured telephone interview was performed using a functional independence measurement-functional activity measurement questionnaire consisting of 30 questions in seven categories (self-care, sphincter control, mobility, locomotion, communication, psychosocial, and cognitive). Each question was scored from 1 (requires full assistance) to 7 (fully independent). Outcomes were compared by type of BCVI, associated injuries, and stroke. RESULTS: Two hundred twenty-two patients with BCVI were identified. Twenty-four patients died during their initial hospitalization, and an additional 11 patient died after hospital discharge. The 68 patients who completed the interview constituted our study population. Mean follow-up was 35 months. Of a possible 210 points, the mean total score on functional independence measurement and functional activity measurement was 186, 185, and 188 for all patients, carotid artery injuries, and vertebral arteries injuries, respectively. A significant difference was seen when comparing patients with and without strokes (173 and 189, respectively). CONCLUSION: This is the first report of functional outcomes following BCVI. We found that carotid and vertebral artery injuries have similar functional outcomes. As would be expected, the development of stroke led to worse outcomes. This underscores the importance of early diagnosis and initiation of therapy. Prevention of stroke in patients with BCVI leads to near-normal functional outcomes. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.
Asunto(s)
Traumatismos Cerebrovasculares/fisiopatología , Cognición/fisiología , Locomoción/fisiología , Heridas no Penetrantes/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Cerebral , Traumatismos Cerebrovasculares/diagnóstico , Traumatismos Cerebrovasculares/epidemiología , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tennessee/epidemiología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/epidemiología , Adulto JovenRESUMEN
A clival epidural hematoma is a rare lesion that usually develops after a hyperflexion or hyperextension injury of the neck, often in a child. A 5-year-old girl presented after a motor vehicle accident with multiple cranial neuropathies, including bilateral abducens nerve pareses and right facial, glossopharyngeal, and hypoglossal cranial nerve palsies. Neuroimaging identified a clival epidural hematoma. The child was observed and the hematoma resolved. The abducens nerve palsies resolved during the ensuing 14 months.
Asunto(s)
Enfermedades del Nervio Abducens/etiología , Traumatismos Cerebrovasculares/complicaciones , Diplopía/etiología , Hematoma Epidural Craneal/etiología , Enfermedades del Nervio Abducens/diagnóstico , Enfermedades del Nervio Abducens/fisiopatología , Accidentes de Tránsito , Traumatismos Cerebrovasculares/fisiopatología , Preescolar , Fosa Craneal Posterior , Diplopía/diagnóstico , Diplopía/fisiopatología , Femenino , Hematoma Epidural Craneal/diagnóstico , Hematoma Epidural Craneal/fisiopatología , Humanos , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X , Agudeza Visual/fisiologíaRESUMEN
Trauma continues to be the leading cause of death in children older than 1 year of age. Although vascular injuries are uncommon, they contribute significantly to the mortality and morbidity related to traumatic injuries in the pediatric age group. In a recently reported large series of children, the head and neck location constituted 19.4% of all pediatric vascular injuries and accounted for most of the mortality observed. Catheter angiography is still considered as the gold standard diagnostic modality. However, because of its invasive nature, other techniques such as computed tomography angiography and magnetic resonance angiography are emerging as alternative diagnostic screening tools. Traumatic vascular injuries can involve the carotid as well as the vertebral arteries. They can be extracranial or intracranial. As a result, traumatic vascular injuries are a heterogeneous group of entities with potential significant implication on the natural history and prognosis. The optimal management of these injuries remains unclear and current practice is largely individualized. This report reviews the available literature regarding the current trends in diagnosis and management of pediatric traumatic vascular injuries.