RESUMEN
Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is the main cause to poor outcomes of SAH patients, and early inflammation plays an important role in the acute pathophysiological events. It has been demonstrated that ethyl pyruvate (EP) has anti-inflammatory and neuroprotective effects in various critical diseases, however, the role of EP on EBI following SAH remains to be elucidated. Our study aimed to evaluate the effects of EP on EBI following SAH in the endovascular perforation rabbit model. All rabbits were randomly divided into three groups: sham, SAH + Vehicle (equal volume) and SAH + EP (30 mg/kg/day). MRI was performed to estimate the reliability of the EBI at 24 and 72 h after SAH. Neurological scores were recorded to evaluate the neurological deficit, ELISA kit was used to measure the level of tumor necrosis factor-α (TNF-α), and western blot was used to detect the expression of TNF-α, tJNK, pJNK, bax and bcl-2 at 24 and 72 h after SAH. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB) staining were used to detect neuronal apoptosis and neurodegeneration respectively, meanwhile hematoxylin and eosin (H&E) staining was used to assess the degree of vasospasm. Our results demonstrated that EP alleviated brain tissue injury (characterized by diffusion weighted imaging and T2 sequence in MRI scan), and significantly improved neurological scores at 72 h after SAH. EP decreased the level of TNF-α and downregulated pJNK/tJNK and bax/bcl-2 in cerebral cortex and hippocampus effectively both at 24 and 72 h after SAH. Furthermore, EP reduced TUNEL and FJB positive cells significantly. In conclusion, the present study supported that EP afforded neuroprotective effects possibly via reducing TNF-α expression and inhibition of the JNK signaling pathway. Therefore, EP may be a potent therapeutic agent to attenuate EBI following SAH.
Asunto(s)
Antiinflamatorios/uso terapéutico , Lesiones Encefálicas/prevención & control , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Piruvatos/uso terapéutico , Hemorragia Subaracnoidea/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/metabolismo , Procedimientos Endovasculares/efectos adversos , Sistema de Señalización de MAP Quinasas/fisiología , Imagen por Resonancia Magnética/métodos , Masculino , Piruvatos/farmacología , Conejos , Distribución Aleatoria , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/metabolismoRESUMEN
Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.
Asunto(s)
Adenosina Monofosfato/farmacología , Hipotermia Inducida , Inflamación/prevención & control , Daño por Reperfusión/terapia , Animales , Apoptosis , Circulación Cerebrovascular , Modelos Animales de Enfermedad , Frecuencia Cardíaca/efectos de los fármacos , Elastasa de Leucocito/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/patología , Daño por Reperfusión/fisiopatología , Receptores Toll-Like/fisiologíaRESUMEN
The objective of this study was to investigate the diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions. A total of 63 patients (45 men and 18 women; mean age of 43 years with a range from 20 to 72 years) who suffered from traumatic bifrontal contusions between January 2007 and December 2012 were inspected. The clinical and imaging results were studied for all patients, and we found that swelling of the mesencephalon and a downward shift of the bilateral red nucleus were significant signs of central brain herniation in the image of magnetic resonance imaging. All patients were given a simultaneous bilateral craniotomy for balanced decompressive surgery. The Glasgow Outcome Scale was used to monitor the patients during the follow-up period, which lasted from 6 to 52 months with a mean of 22 months. At the termination of the follow-up period, the following Glasgow Outcome Scale scores were obtained: 14 patients scored 5 points, 22 patients scored 4 points, 7 patients scored 3 points, 13 patients scored 2 points, and 7 patients scored 1 point. Therefore, our study suggested that an early magnetic resonance imaging scan could result in a more timely diagnosis of central brain herniation, and simultaneous bilateral craniotomy was found to be one of the best treatments for central brain herniation to improve patient outcomes.
Asunto(s)
Lesiones Encefálicas/complicaciones , Encefalocele/diagnóstico , Hueso Frontal/lesiones , Adulto , Anciano , Craneotomía/métodos , Descompresión Quirúrgica/métodos , Diagnóstico Precoz , Encefalocele/etiología , Encefalocele/cirugía , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Escala de Consecuencias de Glasgow , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Mesencéfalo/lesiones , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Núcleo Rojo/lesiones , Tomografía Computarizada por Rayos X/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
Transient forebrain or global ischemia induces neuronal death in vulnerable CA1 pyramidal cells with many features. A brief period of ischemia, i.e., ischemic preconditioning, or a modified reperfusion such as ischemic postconditioning, can afford robust protection of CA1 neurons against ischemic challenge. Therefore, we investigated the effect of ischemic preconditioning and postconditioning on neural cell apoptosis in rats. The result showed that both ischemic preconditioning and postconditioning may attenuate the neural cell death and DNA fragment in the hippocampal CA1 region. Further western blot study suggested that ischemic preconditioning and postconditioning down-regulates the protein of cleaved caspase-3, caspase-6, caspase-9 and Bax, but up-regulates the protein Bcl-2. These findings suggest that ischemic preconditioning and postconditioning have a neuroprotective role on global brain ischemia in rats through the same effect on inhibition of apoptosis.
Asunto(s)
Isquemia Encefálica/patología , Región CA1 Hipocampal/irrigación sanguínea , Poscondicionamiento Isquémico/métodos , Precondicionamiento Isquémico/métodos , Neuronas/citología , Animales , Apoptosis , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Región CA1 Hipocampal/patología , Caspasas/metabolismo , Células Cultivadas , Fragmentación del ADN , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Neuronas/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Live stream services have emerged as a highly profitable Internet application in recent years with rapidly growing audiences for this form of instant and interactive Internet media. This study applies media richness theory along with uses and gratifications theory to predict user loyalty to live stream services. The proposed model is empirically evaluated using survey data collected from 295 users responding about their perception of such services. Empirical results show that perceived media richness and gratifications such as entertainment and sociability are antecedents of loyalty, while immediate feedback is the most salient facet of perceived media richness. The results provide further useful insights for service providers and streamers to build loyal user bases.
Asunto(s)
Medios de Comunicación , Comportamiento del Consumidor , Internet , HumanosRESUMEN
Hemorrhagerelated neurologic injury is a primary cause of disability and mortality following subarachnoid hemorrhage (SAH). The aim of the present study was to investigate the potential neuroprotective effect and the possible role of autophagy in limb remote ischemic postconditioning (RIPostC) using an endovascular puncture rat model of SAH. RIPostC was induced by three cycles of occlusion (10 min) and release (10 min) in the bilateral femoral artery using an aneurysm clip. Early RIPostC began immediately following SAH, delayed RIPostC began following a 30 min delay and the repeated RIPostC group underwent the protocol every day for 3 days. Brain water content, SAH grading, terminal deoxynucleotidyl transferase dUTP nick end labelingDAPI staining, transmission electron microscopy, and neurological and behavioral tests were conducted three days following surgery. Long term outcomes of behavior and memory were assessed using a rotarod test and Morris water maze test 1 month subsequently. Biomarkers of autophagy, including Beclin1 and light chain 3 (LC3), were assessed using western blotting. The results of the present study demonstrated that, compared with other groups, repeated RIPostC was able to alleviate brain edema, prevent neuronal apoptosis, and improve short term and long term neurological function and memory. Beclin1 and LC3 in the cortex were upregulated following treatment with repeated RIPostC. Autolysosomes increased 3 days following SAH and were maintained for 1 month in the repeated RIPostC group. Therefore, the present study indicated that the optimized repeated RIPostC may provide a noninvasive strategy to induce neuroprotection, and improve the short and long term outcomes of SAHrelated cerebral injury, possibly involving the autophagy pathway.
Asunto(s)
Extremidades/irrigación sanguínea , Poscondicionamiento Isquémico , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/rehabilitación , Animales , Apoptosis , Autofagia , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/ultraestructura , Edema Encefálico/metabolismo , Edema Encefálico/patología , Modelos Animales de Enfermedad , Poscondicionamiento Isquémico/métodos , Masculino , Actividad Motora , Neuroprotección , Ratas , Hemorragia Subaracnoidea/etiologíaRESUMEN
Circular RNAs (circRNAs) have been demonstrated to be involved in various biological processes. Nevertheless, the function of circRNAs in medulloblastoma (MB) is still unknown. The present study aimed to investigate the expression profiles of circRNAs and related mechanisms for regulating the proliferation and growth of tumor cells in MB. The expression profiles of circRNAs were screened from four normal cerebellum and four MB samples using a HiSeq Sequencer. Bioinformatic analysis was employed to predict the interaction between circRNAs and mRNAs in MB. Subsequently, the expression levels of eight differential circRNAs [circ-SKA3 (hsa_circ_0029696), circ-DTL (hsa_circ_0000179), circ-CRTAM, circ-MAP3K5 (hsa_circ_0006856), circ-RIMS1-1 (hsa_circ_0132250), circ-RIMS1-2 (hsa_circ_0076967), circ-FLT3-1 (hsa_circ_0100165), and circ-FLT3-2 (hsa_circ_0100168)] were validated using quantitative reverse transcription-polymerase chain reaction. Moreover, circ-SKA3 and circ-DTL were silenced using small interfering RNAs and their host genes were overexpressed to investigate their role in the pathogenesis of MB. A total of 33 circRNAs were found to be differentially expressed in MB tissues (fold change ≥ 2.0, FDR <0.05), of which three were upregulated and 30 were downregulated; six circRNAs were experimentally validated successfully. Upregulated circ-SKA3 and circ-DTL promoted the proliferation migration and invasion in vitro by regulating the expression of host genes. This novel study exploited the profiling of circRNAs in MB and demonstrated that circ-SKA3 and circ-DTL were crucial in the tumorigenesis and development of MB and might be considered as novel and potential biomarkers for the diagnosis and new targets for the intervention of MB.
Asunto(s)
Neoplasias Cerebelosas/genética , Meduloblastoma/genética , ARN , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Cerebelosas/patología , Cerebelo/metabolismo , Regulación hacia Abajo , Humanos , Meduloblastoma/patología , ARN Circular , ARN Mensajero , Regulación hacia ArribaRESUMEN
Xenon (Xe), a noble gas, has promising neuroprotective properties with no proven adverse side-effects. We evaluated neuroprotective effects of Xe delivered by Xe-containing echogenic liposomes (Xe-ELIP) via ultrasound-controlled cerebral drug release on early brain injury following subarachnoid hemorrhage (SAH). The Xe-ELIP structure was evaluated by ultrasound imaging, electron microscopy and gas chromatography-mass spectroscopy. Animals were randomly divided into five groups: Sham, SAH, SAH treated with Xe-ELIP, empty ELIP, or Xe-saturated saline. Treatments were administrated intravenously in combination with ultrasound application over the common carotid artery to trigger Xe release from circulating Xe-ELIP. Hematoma development was graded by SAH scaling and quantitated by a colorimetric method. Neurological evaluation and motor behavioral tests were conducted for three days following SAH injury. Ultrasound imaging and electron microscopy demonstrated that Xe-ELIP have a unique two-compartment structure, which allows a two-stage Xe release profile. Xe-ELIP treatment effectively reduced bleeding, improved general neurological function, and alleviated motor function damage in association with reduced apoptotic neuronal death and decreased mortality. Xe-ELIP alleviated early SAH brain injury by inhibiting neuronal death and bleeding. This novel approach provides a noninvasive strategy of therapeutic gas delivery for SAH treatment.
Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Fármacos Neuroprotectores/administración & dosificación , Hemorragia Subaracnoidea/tratamiento farmacológico , Xenón/administración & dosificación , Administración Intravenosa , Animales , Lesiones Encefálicas/diagnóstico por imagen , Lesiones Encefálicas/etiología , Modelos Animales de Enfermedad , Liberación de Fármacos , Liposomas/administración & dosificación , Liposomas/química , Microscopía Electrónica de Transmisión , Fármacos Neuroprotectores/farmacocinética , Distribución Aleatoria , Ratas , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico por imagen , Ultrasonografía , Xenón/farmacocinéticaRESUMEN
Ischemic postconditioning, including early and delayed ischemic postconditioning, has been recognized as a simple and promising strategy in the treatment of stroke. However, the effects of the combination of early and delayed ischemic postconditioning, and the mechanisms underlying these effects, remain unclear. The aim of the present study was to determine whether the combination of early and delayed ischemic postconditioning offers greater protection against stroke, and enhances the production of brainderived neurotrophic factor (BDNF). A combination of early and delayed ischemic postconditioning was established by repeated, transient occlusion and reperfusion of the ipsilateral common carotid artery in a rat model of middle cerebral artery occlusion. Infarct size, motor function, cerebral blood flow and brain edema were then evaluated, in order to confirm the effects of combinative ischemic postconditioning. TUNEL staining was used to analyze the rate of apoptosis of cells in the penumbral area. BDNF, extracellular signalregulated kinases 1/2 (ERK1/2) and cAMP response elementbinding protein (CREB) expression was detected using immunofluorescence staining and western blot analysis. The results of the present study indicated that the combination of early and delayed ischemic postconditioning further reduced the infarct volume, stabilized cerebral blood disturbance and attenuated neuronal apoptosis, compared with either alone. However, combinative postconditioning exerted the same effect on neurological function and brain edema, compared with early or delayed ischemic postconditioning alone. Further investigation indicated that combinative ischemic postconditioning increased the expression of BDNF, and a significantly higher number of BDNFpositive cells was observed in neurons and astrocytes from the combined group than in the early or delayed groups. Combinative ischemic postconditioning also induced the phosphorylation of ERK1/2 and CREB in the cortex, following focal ischemia. The results of the present study suggest that the combination of early and delayed ischemic postconditioning may further reduce brain ischemic reperfusion injury following focal ischemia, compared with either treatment alone. In addition, it induces the production of BDNF in neurons and astrocytes. Furthermore, the effects of combinative ischemic postconditioning may be mediated by the activation of ERK1/2 and CREB.