Characterization of neonatal seizures in an animal model of hypoxic-ischemic encephalopathy

In this study, we use time-locked video and electroencephalography (EEG) recordings to characterize acute seizures and EEG abnormalities in an animal model that replicates many salient features of human neonatal hypoxic-ischemic encephalopathy (HIE) including the brain injury pattern and long-term neurologic outcome.

Hypoxia-ischemia (HI) was induced in 7-day-old rats by ligating the right carotid artery and exposing the pups to hypoxia for 2 h (Rice-Vannucci method). To identify seizures and abnormal EEG activity, pups were monitored by video-EEG during hypoxia and at various time points after HI. Occurrence of electroclinical seizures, purely electrographic seizures and other abnormal discharges on EEG, was quantified manually. A power spectrum analysis was done to evaluate the effects of HI on EEG spectra in the 1-50 Hz frequency band.

During hypoxia, all pups exhibit short duration, but frequent electroclinical seizures. Almost all pups continue to have seizures in the immediate period following termination of hypoxia. In more than half of the HI rats, seizures persisted for 24 h; for some of them, the seizures continued for >48 h. Seizures were not observed in any rats at 72 h after HI induction. A significant reduction in background EEG voltage in the cortex ipsilateral to the ligated carotid artery occurred in rats subjected to HI. In addition, purely electrographic seizures, spikes, sharp waves, and brief runs of epileptiform discharges (BREDs) were also observed in these rats.

HI induction in P7 rats using the Rice-Vannucci method resulted in the development of seizures and EEG abnormalities similar to that seen in human neonates with HIE. Therefore, we conclude that this is a valid model to test the efficacy of novel interventions to treat neonatal seizures.