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OBJECTIVE Connexin hemichannels can open during ischemia, resulting in loss of membrane potential, calcium influx, and release of glutamate. In this study, we tested the hypothesis that opening of hemichannels after cerebral ischemia may contribute to delayed evolution of injury. METHODS We infused a mimetic peptide that blocks connexin 43 hemichannels(More)
Cerebral palsy is one of the most devastating consequences of brain injury around the time of birth, and nearly a third of cases are now associated with premature birth. Compared with term babies, preterm babies have an increased incidence of complications that may increase the risk of disability, such as intraventricular hemorrhage, periventricular(More)
Preterm born infants have high rates of brain injury, leading to motor and neurocognitive problems in later life. Infection and resulting inflammation of the fetus and newborn are highly associated with these disabilities. However, there are no established neuroprotective therapies. Microglial activation and expression of many cytokines play a key role in(More)
Maternal treatment with synthetic corticosteroids such as dexamethasone (DEX)significantly reduces neonatal morbidity and mortality, but its effects on the fetal brain remain unclear. In this study we evaluated the effects of DEX on EEG activity in preterm fetal sheep. Ewes at 103 days gestation received two intramuscular injections of DEX (12 mg, n = 8) or(More)
Acute, high-dose exposure to endotoxin lipopolysaccharide (LPS) in preterm fetal sheep can trigger periventricular white matter lesions (PVL), in association with severe hypotension/hypoxemia and significant mortality. Intriguingly, however, chronic or repeated exposure to LPS can induce tachyphylaxis. We therefore tested the hypothesis that progressive,(More)
INTRODUCTION This study examined whether spectral analysis of the electroencephalogram (EEG) can discriminate between mild and severe hypoxic-ischemic injury in the immature brain. RESULTS Total EEG power was profoundly suppressed after umbilical cord occlusion and recovered to baseline by 5 h after 15-min of occlusion, in contrast with transient recovery(More)
Late preterm infants, born between 34 and 36 weeks gestation, have significantly higher morbidity than neonates born at full term, which may be partly related to reduced sensitivity of the arterial baroreflex. The present study assessed baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) in near-term fetal sheep at 123 ± 1 days(More)
Fetuses at risk of premature delivery are now routinely exposed to maternal treatment with synthetic glucocorticoids. In randomized clinical trials, these substantially reduce acute neonatal systemic morbidity, and mortality, after premature birth and reduce intraventricular hemorrhage. However, the overall neurodevelopmental impact is surprisingly unclear;(More)
Preterm infants have a high rate of neurodevelopmental handicap. Recent imaging studies have revealed that adverse outcomes are strongly associated with reduced brain growth and neural complexity in later life. Increasing data suggest that these chronic deficits primarily reflect acute neuronal and glial injury sustained during adverse in utero events, such(More)
Therapeutic hypothermia can partially reduce long-term death and disability in neonates after hypoxic-ischemic encephalopathy. The aim of this study was to determine whether prolonging the duration of cooling from 3 days to 5 days could further improve outcomes of cerebral ischemia in near-term fetal sheep. Fetal sheep (0.85 gestation) received 30 minutes(More)