Interferon-β attenuates lung inflammation following experimental subarachnoid hemorrhage

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) affects relatively young people and carries a poor prognosis with a case fatality rate of 35%. One of the major systemic complications associated with SAH is acute lung injury (ALI) which occurs in up to one-third of the patients and is associated with poor outcome. ALI in SAH may be predisposed by neurogenic pulmonary edema (NPE) and inflammatory mediators. The objective of this study was to assess the immunomodulatory effects of interferon-β (IFN-β) on inflammatory mediators in the lung after experimental SAH. METHODS: Male Wistar rats were subjected to the induction of SAH by means of the endovascular filament method. Sham-animals underwent sham-surgery. Rats received IFN-β for four consecutive days starting at two hours after SAH induction. After seven days, lungs were analyzed for the expression of inflammatory markers. RESULTS: SAH induced the influx of neutrophils into the lung, and enhanced expression of the pulmonary adhesion molecules E-selectin, inter-cellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 compared to sham-animals. In addition, SAH increased the expression of the chemokines macrophage inflammatory protein (MIP)-1α, MIP-2, and cytokine-induced neutrophil chemoattractant (CINC)-1 in the lung. Finally, tumor necrosis factor-α (TNF-α) was significantly increased in lungs from SAH-animals compared to sham-animals. IFN-β effectively abolished the SAH-induced expression of all pro-inflammatory mediators in the lung. CONCLUSIONS: IFN-β strongly reduces lung inflammation after experimental SAH and may therefore be an effective drug to prevent SAH-mediated lung injury

Experimental focal neocortical epilepsy is associated with reduced white matter volume growth : results from multiparametric MRI analysis

Focal epilepsy has recently been associated with remote white matter damage, including reduced white matter volume. Longitudinal assessment of these white matter changes, in relation to functional mechanisms and consequences, may be ideally done by in vivo neuroimaging in well-controlled experimental animal models. We assessed whether advanced machine learning algorithm models could accurately detect volumetric changes in white matter from multiparametric MR images, longitudinally collected in a neocortical focal epilepsy rat model. We measured classification accuracy in two supervised segmentation models: i.e. the generalized linear model and the nonlinear random forest model-by comparing computed white matter probabilities with actual neuroanatomically identified white matter. We found excellent overall discriminatory power for both models. However, the random forest model demonstrated a superior goodness-of-fit calibration plot that was close to the ideal calibration line. Based on this model, we measured that total white matter volume increased in young adult control and epileptic rats over a period of 10 weeks, but the average white matter volume was significantly lower in the focal epilepsy group. Changes in gray matter volume were not significantly different between control and epileptic rats. Our results (1) indicate that recurrent spontaneous seizures have an adverse effect on global white matter growth and (2) show that individual whole brain white matter volume can be accurately determined using a combination of multiparametric MRI and supervised segmentation models, offering a powerful tool to assess white matter volume changes in preclinical studies of neurological disease

Effect of interferon-β on neuroinflammation, brain injury and neurological outcome after experimental subarachnoid hemorrhage

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) has a poor outcome, particularly attributed to progressive injury after the initial incident. Several studies suggest a critical role for inflammation in lesion progression after SAH. Our goal was to test whether treatment with anti-inflammatory interferon-β, which has shown promise as a therapeutic agent in experimental ischaemic stroke, can protect the brain after SAH. METHODS: SAH was induced in adult male Wistar rats by puncturing the intracranial bifurcation of the right internal carotid artery. Treatment effects of daily interferon-β (n = 16) or vehicle (n = 14) injections were serially evaluated with multiparametric MRI and behavioral tests from day 0 to 7, in compliance with recent recommendations for pre-clinical drug testing. Outcome measures included neurological status, brain lesion volume, blood-brain barrier (BBB) leakage, and levels of inflammatory markers. RESULTS: In animals that survived up to 7 days post-SAH, we found no significant differences between vehicle- and interferon-β-treated animals with respect to final neurological score (14.3 ± 1.0 vs. 13.0 ± 2.2), brain lesion size on T(2)-weighted MR images (59 ± 83 vs. 124 ± 99 mm(3)), BBB leakage (0.26 ± 0.05 vs. 0.22 ± 0.08 contrast-induced relative MR signal change), upregulation of brain RNA for cytokines, chemokines and cell adhesion molecules, and increased neutrophil activation. CONCLUSIONS: In contrast to previously published findings in experimental ischemic stroke models, interferon-β has no clear efficacy to protect the brain after SAH. In line with recent highlighting of the significance of negative findings, our data currently do not recommend clinical testing of interferon-β to prevent neurological damage in SAH patients

Hypoxia-related microRNA-210 is a diagnostic marker for discriminating osteoblastoma and osteosarcoma

© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. Osteoblastoma is a benign bone tumor that can often be difficult to distinguish from malignant osteosarcoma. Because misdiagnosis can result in unfavorable clinical outcomes, we have investigated microRNAs as potential diagnostic biomarkers for distinguishing between these two tumor types. Next generation RNA sequencing was used as an expression screen to evaluate >2,000 microRNAs present in tissue derived from rare formalin fixed paraffin embedded (FFPE) archival tumor specimens. MicroRNAs displaying the greatest ability to discriminate between these two tumors were validated on an independent tumor set, using qPCR assays. Initial screening by RNA-seq identified four microRNA biomarker candidates. Expression of three miRNAs (miR-451a, miR-144-3p, miR-486-5p) was higher in osteoblastoma, while the miR-210 was elevated in osteosarcoma. Validation of these microRNAs on an independent data set of 22 tumor specimen