Abstracts

Rationale: Hypoxic-ischemic encephalopathy (HIE) is one of the most common causes of seizures in full-term infants. Studies in both human neonates and animal models suggest that seizures themselves may independently contribute to brain injury and poor neurological outcome. Hypoxia-Ischemia (HI) induced injury in neonatal rats is a commonly used model to study acute as well as chronic changes caused by HIE. In the current study, we characterize HI-induced acute neonatal seizures and changes in the EEG in an animal model of HIE. Methods: Sprague-Dawley rat pups were implanted with bilateral sub-dural electrodes on postnatal day 6 (P6). To induce HI, the right carotid artery of P7 pups was ligated and the pups were then exposed to hypoxia in an 8% oxygen environment for 2 hours. Rats were video EEG (VEEG) monitored before HI, during hypoxia exposure, immediately after hypoxia and 24 hours after HI. Electroclinical seizures were defined as an EEG pattern that differs from background in either / or both amplitude and frequency, evolves over time, contains spikes or sharps lasting for 10 seconds or more and is associated with a change in the rat's behavior. Electrographic seizures were those observed on EEG that were not associated with changes in rat behavior. Electrographic discharges were defined as EEG patterns similar to those in electrographic seizures, but lasting less than 10 seconds. These may or may not be associated with a change in the rat's behavior. Results: Analysis of VEEG recordings revealed that the rat pups exhibit multiple electroclinical seizures during 2 hours of hypoxia (mean ± SD = 13.25 ± 1.7; n = 4). The first electroclinical seizure was observed 11.07 + 11.39 minutes (mean ± SD; n=5) after initiation of hypoxia. The total duration of electroclinical seizures during 2 hours of hypoxia was 9.03 + 4.1 minutes (mean ± SD; n = 4). Multiple electrographic discharges and myoclonic jerks were also observed during hypoxia. In only one rat, electrographic seizures (without clinical correlate) were observed during hypoxia (n = 4). HI rat pups have multiple acute post-hypoxia seizures and seize 26.1% of the time in the first 2 hours after hypoxia (n = 4). Twenty-four hours after HI, one rat was observed to have electroclinical seizures (n = 2). Behavioral seizures included forelimb and hindlimb clonus, vibratory tonic seizures, whole body jerks, forelimb jerks, facial automatisms, tail stiffening, forelimb and hindlimb paddling, thrashing and circling. Power spectrum analysis showed suppression of EEG activity at lower frequencies (3-20 Hz) in both cortices during hypoxia (p<0.04; paired t-test). The EEG power returned to baseline values after hypoxia i.e., during the reperfusion period. Conclusions: In this model of neonatal HI, we found that rats have multiple seizures during and immediately after hypoxia. We also note a decrease in power in the EEG during hypoxia, likely due to the suppression of the normal background rhythms in the rats. This is similar to the suppression noted in humans following neonatal HI.