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Neurobiol Dis. 2018 Aug;116:1-12. doi: 10.1016/j.nbd.2018.04.012. Epub 2018 Apr 21.

Sleep dysfunction following neonatal ischemic seizures are differential by neonatal age of insult as determined by qEEG in a mouse model.

Author information

1
Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Johns Hopkins University, Baltimore, MD 21205, USA.
2
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
3
Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Johns Hopkins University, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Pediatrics, Johns Hopkins University School of Medicine; Baltimore, MD 21205, USA.
4
Department of Neuroscience, Hugo Moser Research Institute at Kennedy Krieger, Johns Hopkins University, Baltimore, MD 21205, USA; Departments of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: kadam@kennedykrieger.org.

Abstract

Neonatal seizures associated with hypoxic-ischemic encephalopathy (HIE) pose a challenge in their acute clinical management and are often followed by long-term neurological consequences. We used a newly characterized CD-1 mouse model of neonatal ischemic seizures associated with age-dependent (P7 vs. P10) seizure severity and phenobarbital efficacy (i.e.; PB-resistant vs. PB-efficacious respectively) following unilateral carotid ligation. The long-term consequences following untreated neonatal seizures in P7 vs. P10 ligated pups were investigated using neurobehavioral testing, 24 h v- quantitative EEG -EMG (qEEG, qEMG), and western blot analyses in adult mice. Significant hyperactivity emerged in a small sub-set of mice in both age-groups associated with a failure to habituate during open-field (OF) testing. 24 h continuous qEEGs detected significantly altered sleep architecture due to long-wake cycles in both age-groups. Delta power (0.5-4 Hz) quantification during slow-wave-sleep (SWS) revealed significant SWS compensation in P10 ligates following periods of increased sleep pressure which the P7 ligate group failed to show. Theta/beta ratios deemed as negative correlation markers of attentional control were significantly higher only in the P10 ligates. These results indicate that neonatal age-dependent differences in the characteristics of ischemic neonatal seizures in CD-1 pups differentially modulate long-term outcomes, when evaluated with v-qEEG/EMG as adults.

KEYWORDS:

Delta power; Hyperactivity; Hypoxic-ischemic encephalopathy; Ischemia; Neonatal seizures; Sleep structure

PMID:
29684437
PMCID:
PMC5995660
[Available on 2019-08-01]
DOI:
10.1016/j.nbd.2018.04.012

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