High cerebrospinal fluid antioxidants and interleukin 8 are protective of hypoxic brain damage in newborns
ABSTRACT 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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- "The trial revealed no significant effects of minocycline on the profile of immune mediators implicated in inflammatory mechanisms in either the serum or CSF of treated children with the exception of a reduction in the levels of CXCL8 (IL-8), a chemokine that appears to have neuroprotective effects  and regulates the release of MMPs . A hypothesized reduction of immune modulators associated with monocyte trafficking or microglia function such as CCL2 (MCP-1) or certain MMPs, was not proven by this clinical trial. "
ABSTRACT: BACKGROUND: Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression. METHODS: Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation. RESULTS: Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and alpha-2 macroglobulin (alpha-2 M), was also significantly lower (P = 0.028) while the mature BDNF/alpha-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-alpha, CD40L, IL-6, IFN-gamma and IL-1beta when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline. CONCLUSIONS: Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration. .Trail registration: NCT00409747.Journal of Neurodevelopmental Disorders 04/2013; 5(1):9. DOI:10.1186/1866-1955-5-9 · 3.71 Impact Factor
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- "It should also be considered the possibility that 6OHMS we measured after EMF exposure is not due to an alteration of melatonin production, but of its metabolism in the liver where about 70–80% of the circulating melatonin is metabolized first to 6-hydroxy-melatonin, then to 6OHMS . Melatonin is a free-radical scavenger   , therefore it is important to prevent several health problems to the newborns, that the excess of free-radicals can provoke  . Then, a source of altered melatonin production can have unknown consequences on health. "
ABSTRACT: During permanence in most incubators, newborns are very close to the electric engine, which represents a source of electromagnetic fields (EMF). Previous studies demonstrated a decrease in melatonin production in adults and animals exposed to EMF. To assess melatonin production in a group of newborns exposed to EMF, and to evaluate whether removing the babies from the source of MF can affect melatonin production. We have recruited 28 babies (study group), who had spent at least 48 h in incubator where we had previously assessed the presence of significant EMF. We have measured their mean 6-hydroxy-melatonin-sulfate (6OHMS) urine excretion at the end of their permanence in the incubators, and compared it with their mean 6OHMS excretion after having been put in cribs, where EMF are below the detectable limit (<0.1mG). We have also measured urine 6OHMS twice, with an interval of 48h, in a control group of 27 babies who were not exposed to EMF during both samples. Mean 6OHMS/cr values were respectively 5.34±4.6 and 7.68±5.1ng/mg (p=0.026) when babies were exposed to EMF in incubators, and after having been put in the crib. In the control group, mean 6OHMS/cr values in the first and in the second sample were respectively 5.91±5.41 vs 6.17±3.94ng/mg (p=0.679). The transitory increase in melatonin production soon after removing newborns from incubators demonstrates a possible influence of EMF on melatonin production in newborns. Further studies are needed to confirm these data.Early human development 03/2012; 88(8):707-10. DOI:10.1016/j.earlhumdev.2012.02.015 · 1.93 Impact Factor
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ABSTRACT: Systemic infection in the newborn (neonatal sepsis) is the most common cause of neonatal mortality. Neonatal sepsis is complicated by pulmonary hypertension. In this study, we analyzed the effect of edaravone, a free radical scavenger that is known to reduce the production of inflammatory mediators, such as tumor necrosis factor α (TNFα), on pulmonary hypertension. Experimental and sham groups were drawn from 19 three-day-old piglets; 5 underwent a modified procedure of cecal ligation and perforation (CLP) (CLP group), 8 underwent CLP followed 30 min later by edaravone intravenous administration (edaravone group), and 6 did not undergo CLP and did not receive edaravone (sham group). To evaluate the pulmonary blood pressure despite the sepsis-induced low cardiac output, mean arterial blood pressure (mABP), mean pulmonary arterial pressure (mPAP), and comparative pulmonary hypertension ratio (mPAP/mABP) were determined. Serum TNFα levels were measured before the procedure and at 1, 3, and 6 h after. The mPAP levels were higher in the CLP group at 9 h compared to the edaravone group. The mPAP/mABP ratio was lower in the edaravone and sham groups compared to the CLP group at 6 and 9 h. TNFα in the edaravone and sham groups were lower at 1 and 3 h compared to that in the CLP group. In all animals, mPAP/mABP at 6 h correlated with serum levels of TNFα at 1, 3, and 6 h. These findings suggest that edaravone ameliorates the severity of pulmonary hypertension in a neonatal sepsis model by reducing serum TNFα levels.The Tohoku Journal of Experimental Medicine 01/2011; 223(4):235-41. DOI:10.1620/tjem.223.235 · 1.28 Impact Factor