Predictive value of early EEG for seizures in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.

OBJECTIVES: To assess the prognostic significance of an early normal/mildly abnormal conventional EEG (cEEG) on seizure risk in neonates undergoing therapeutic hypothermia. METHODS: We reviewed the video-EEG recordings from a large cohort of neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy from 2008 to 2017 in a single tertiary center. Continuous video-EEG was started as soon as possible (median 8.2 h) and continued throughout hypothermia and rewarming. We studied those neonates with a normal/mildly abnormal EEG during the first 24 h of monitoring. RESULTS: A total of 331 neonates were treated with hypothermia and 323 had cEEG recordings available for review; 99 were excluded because of a moderately/severely abnormal cEEG background and/or seizure during the first 24 h of recording, and an additional eight because of early rewarming. The remaining 216 had a normal/mildly abnormal cEEG in the first 24 h. None of these patients subsequently developed seizures. CONCLUSION: A normal/mildly abnormal cEEG during the first 24 h indicates a very low risk of subsequent seizures. This suggests that cEEG monitoring can be safely discontinued after 24 h if it has remained normal or excessively discontinuous and no seizures are detected, limiting the need for this resource-intensive and expensive tool.

Efferocytosis Mediated Modulation of Injury after Neonatal Brain Hypoxia-Ischemia.

Neonatal brain hypoxia-ischemia (HI) is a leading cause of morbidity and long-term disabilities in children. While we have made significant progress in describing HI mechanisms, the limited therapies currently offered for HI treatment in the clinical setting stress the importance of discovering new targetable pathways. Efferocytosis is an immunoregulatory and homeostatic process of clearance of apoptotic cells (AC) and cellular debris, best described in the brain during neurodevelopment. The therapeutic potential of stimulating defective efferocytosis has been recognized in neurodegenerative diseases. In this review, we will explore the involvement of efferocytosis after a stroke and HI as a promising target for new HI therapies.

A role for hypoxia-inducible factor-1alpha in desferoxamine neuroprotection.

The newborn brain has increased vulnerability to hypoxia-ischemia from maturational differences in the oxidative stress response. We hypothesized that desferoxamine (DFO), an iron chelator, would provide protection in an in vitro model of ischemia in part through activation of the hypoxia-inducible gene hypoxia-inducible factor-1alpha (HIF-1alpha). Hippocampal neurons from E16 CD1 mice were exposed to 3 h of oxygen and glucose deprivation with and without pretreatment with 10 mmol/L DFO in the presence and absence of 2 micromol/L antisense oligonucleotides specific for HIF-1alpha (antiHIF-1alpha). DFO pretreatment resulted in 45% reduction in cell death (p = 0.006). This protection was diminished with transfection of antiHIF-1alpha (p = 0.049). Blocking HIF-1alpha reduces DFO protection suggesting that DFO protects through iron chelation and HIF-1alpha induction.