The hypoxia-responsive cytokine erythropoietin (EPO) provides neuroprotective effects in the damaged brain during ischemic events and neurodegenerative diseases. The purpose of the present study is to evaluate the EPO/EPO receptor (EPOR) endogenous system between astrocyte and oligodendrocyte precursor cell (OPC) under hypoxia. We report here elevated EPO mRNA levels and protein release in cultured astrocytes following hypoxic stimulation by quantitative RT-PCR and ELISA. Furthermore, the EPOR gene expressions were detected in cultured OPCs as in astrocytes and microglias by quantitative RT-PCR. Cell staining revealed the EPOR expression in OPC. To evaluate the protective effect of endogenous EPO from astrocyte to OPCs, EPO/EPOR signaling was blocked by EPO siRNA or EPOR siRNA gene silencing in in vitro study. The suppression of endogenous EPO production in astrocytes by EPO siRNA decreased the protection to OPCs against hypoxic stress. Furthermore, OPC with EPOR siRNA had less cell survival after hypoxic/reoxygenation injury. This suggested that EPO/EPOR signaling from astrocyte to OPC could prevent OPC damage under hypoxic/reoxygenation condition. Our present finding of an interaction between astrocytes and OPCs may lead to a new therapeutic approach to OPCs for use against cellular stress and injury.
BackgroundAlthough aneurysmal bone cysts (ABCs) are benign tumours, they have the potential to be locally aggressive. Various treatment approaches, such as en bloc resection, open curettage, radiotherapy, sclerotherapy, and embolization have been proposed, but the most appropriate treatment should be selected after considering the risk of tumour recurrence and treatment complications. Endoscopic curettage (ESC) may be a less invasive alternative to open curettage for ABC treatment. We aimed to describe the use of ESC for the treatment of ABCs and to report our clinical outcomes, including the incidence rate of recurrence, radiological appearance at final follow-up, time to solid union, complications, and postoperative function.MethodsBetween 1998 and 2015, 30 patients (18 men and 12 women; mean age, 17.4 years) underwent ESC for the treatment of primary ABCs at our hospital (mean postoperative follow-up, 55 months). ESC was performed under arthroscopic guidance for direct visualization, and curettage extended until normal bone was observed in the medullary cavity. To investigate bone healing after ESC, we evaluated the consolidation of cysts at the final evaluation (based on the modified Neer classification) and time to solid union after surgery, which was defined as sufficient cortical bone thickness to prevent fracture and allow physical activities.ResultsRecurrence was identified in 3 cases (10%). Curative outcomes were obtained after repeated ESC or open curettage. A log-rank analysis indicated that age < 10 years (p = 0.004) and contact of the tumour with the physis (p = 0.01) increased the risk of tumour recurrence. Residual tumours were identified in 9 cases (30%); these lesions remained inactive over the extended follow-up period. The average time to solid union after endoscopic curettage was 3.2 months. Transient radial nerve palsy was identified in 1 case. Good postoperative functional recovery occurred in all cases.ConclusionsESC is a minimally invasive technique for the treatment of ABCs, and the tumour recurrence rate is comparable to that of other standard procedures. However, the application of this method should be carefully considered, especially for patients < 10 years and when the tumour comes in contact with the physis.Electronic supplementary materialThe online version of this article (10.1186/s12891-018-2176-6) contains supplementary material, which is available to authorized users.
Free radicals play an important role in the inflammatory process of sepsis. We hypothesized that edaravone, a novel free radical scavenger, can suppress pathophysiological events and prolong survival in a neonatal sepsis cecal ligation and perforation (CLP) model. Of 32 3-day-old anesthetized and mechanically ventilated piglets, 11 received CLP only, 10 received CLP and edaravone treatment starting 30 min after CLP, and 11 constituted a sham (control) group. Mean arterial pressure (MAP), heart rate, cardiac output, arterial blood gas, serum total hydroperoxide, nitrite and nitrate, TNF-alpha, and high-mobility group box 1 (HMGB1) were measured before CLP and at 1, 3, and 6 h after CLP. Compared with the CLP group, the edaravone group showed higher MAP at 6 h, lower heart rate at 1 and 3 h, lower total hydroperoxide at 1 h, lower nitrite and nitrate at 3 and 6 h, and higher (although not significantly so) mean cardiac output at 1, 3, and 6 h. TNF-alpha elevation was delayed from 1 h in the CLP group to 3 h in the edaravone group. In the edaravone group, HMGB1 did not change significantly at any time, whereas in the CLP group, it increased at 6 h. Survival times were longer in the edaravone group than in the CLP group (15.4 +/- 1.4 vs. 10.2 +/- 1 h; P < 0.005). In addition, each of the serial dilutions of edaravone had a higher biological antioxidant potential than tempol does. In conclusion, edaravone suppressed free radicals, delayed the TNF-alpha surge, and prevented HMGB1 elevation, thereby maintaining MAP and prolonging survival time in a neonatal sepsis CLP model.
ETR-P1/fl treatment significantly attenuated the elevation of NOx, TNF-α, and HMGB-1, which improved the systemic hypotension, pulmonary hypertension, and blood gases, thereby causing improvement of survival time in a progressive neonatal sepsis CLP model.
The objective was to explain the discrepancy in the development of hypoxic ischemic brain injury (HIE) in some asphyxiated newborns rather than others. Forty newborns were classified according to their cerebrospinal neuron-specific-enolase (CSF-NSE) levels on their 5th-day of life; group 1 with low-NSE (n = 25). The remaining 15 newborns had high-NSE and were further divided into a group with no HIE (n = 10, group 2) and another with HIE (n = 5, group 3). CSF-NSE, total-hydroperoxide (TH), biological-antioxidant-potentials (BAPs), 12 cytokines and erythropoietin (EPO) were measured. The TH/BAP gave the oxidative-stress-index (OSI). The BAPs of serial dilutions of three types of EPO were tested. CSF-NSE and TH and mean OSIs were higher in group 3. IL-8 and mean BAPs were higher in group 2 than in group 1. EPO was less detected in group 3. Serial EPO dilutions correlated with their BAPs. Compensatory antioxidants and IL-8 elevation could be protective of perinatal asphyxic brain injury. Antioxidative effect of EPO could be neuroprotective.
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