RESUMEN
Ischemic stroke is a leading cause of death and disability worldwide. Several reports suggest that acute inflammation after ischemia-reperfusion exacerbates brain damage; however, molecular mechanisms underlying this effect remain unclear. Here, we report that MAC-3-positive immune cells, including infiltrating bone marrow-derived macrophages and activated microglia, express abundant angiopoietin-like protein (ANGPTL) 2 in ischemic mouse brain in a transient middle cerebral artery occlusion (MCAO) model. Both neurological deficits and infarct volume decreased in transient MCAO model mice established in Angptl2 knockout (KO) relative to wild-type mice. Acute brain inflammation after ischemia-reperfusion, as estimated by expression levels of pro-inflammatory cytokines such as interleukin (IL)-1ß and tumor necrosis factor alpha (TNF)-α, was significantly suppressed in Angptl2 KO compared to control mice. Moreover, analysis employing bone marrow chimeric models using Angptl2 KO and wild-type mice revealed that infiltrated bone marrow-derived macrophages secreting ANGPTL2 significantly contribute to acute brain injury seen after ischemia-reperfusion. These studies demonstrate that infiltrating bone marrow-derived macrophages promote inflammation and injury in affected brain areas after ischemia-reperfusion, likely via ANGPTL2 secretion in the acute phase of ischemic stroke.
Asunto(s)
Angiopoyetinas/genética , Encéfalo/metabolismo , Encéfalo/patología , Daño por Reperfusión/genética , Daño por Reperfusión/patología , Proteína 2 Similar a la Angiopoyetina , Proteínas Similares a la Angiopoyetina , Animales , Biomarcadores , Encéfalo/irrigación sanguínea , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Línea Celular , Citocinas/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Inmunohistoquímica , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Noqueados , Modelos Biológicos , Neuronas/metabolismo , Neuronas/patología , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: Evaluating cerebrovascular reserve (CVR) is important for patients with moyamoya disease (MMD). 123I-iodoamphetamine single-photon emission CT (SPECT) with acetazolamide (ACZ) challenge is widely carried out, but using ACZ becomes problematic owing to its off-label use and its adverse effects. Here, we report the efficacy of dynamic susceptibility contrast MRI (DSC-MRI) for the evaluation of CVR in MMD patients. METHODS: All 33 MMD patients underwent both SPECT and DSC-MRI at an interval of <10 days from each other (mean age 38.3 years). The region of interest (ROI) was the anterior cerebral artery (ACA) territory, middle cerebral artery (MCA) territory, basal ganglia and cerebellum hemisphere for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) images. The ratios of the ROIs to the ipsilateral cerebellum were calculated for each parameter and evaluated. The CVR was calculated using images acquired by SPECT before and after ACZ administration. The ratios of DSC-MRI parameters and CVR were compared and evaluated for each ROI. RESULTS: The MTT of the ACA and MCA territories significantly correlated with CVR (p < 0.0001). However, CBF and CBV had no correlation with CVR. The MTT ratio had a threshold of 1.966, with a sensitivity of 68.4% and a specificity of 91.5% for predicting decreased CVR (<10%). CONCLUSION: MTT had a negative correlation with CVR. DSC-MRI is easy, safe and useful for detecting decreased CVR and can be used as a standard examination in MMD patient's care.
Asunto(s)
Circulación Cerebrovascular , Medios de Contraste/administración & dosificación , Gadolinio DTPA/administración & dosificación , Imagen por Resonancia Magnética , Enfermedad de Moyamoya/diagnóstico por imagen , Imagen de Perfusión/métodos , Adolescente , Adulto , Área Bajo la Curva , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/fisiopatología , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Tomografía Computarizada de Emisión de Fotón Único , Adulto JovenRESUMEN
BACKGROUND: Spontaneous superficial temporal artery (STA) pseudoaneurysms are very rare; only four cases, including ours, have been reported to date. Therefore, the cause of them has not been studied. CASE DESCRIPTION: A 57-year-old woman was admitted to our hospital with a pulsatile mass in the left preauricular region. Her medical history included hypertension, dyslipidemia, and angina pectoris. She denied a history of head injury or minor head trauma. Three-dimensional computed tomography angiography showed a well-enhanced saccular aneurysm on the main trunk of the STA. To prevent rupture it was removed surgically. The histological diagnosis was pseudoaneurysm with atherosclerosis. By the 2(nd) postoperative day, she had completely recovered and was discharged home. There has been no relapse. CONCLUSIONS: As all four documented patients were at high risk for atherosclerosis, we posit that a causal factor was weakening of the arterial wall due to atherosclerosis and chronic pressure on the STA from anatomical structures. Here, we present histological evidence to support this hypothesis.
