Ischemic injury suppresses hypoxia-induced electrographic seizures and the background EEG in a rat model of perinatal hypoxic-ischemic encephalopathy

Abstract

Zayachkivsky A, Lehmkuhle MJ, Ekstrand JJ, Dudek FE. Ischemic injury suppresses hypoxia-induced electrographic seizures and the background EEG in a rat model of perinatal hypoxic-ischemic encephalopathy. J Neurophysiol 114: 2753-2763, 2015. First published September 9, 2015 doi:10.1152/jn.00796.2014.-The relationship among neonatal seizures, abnormalities of the electroencephalogram (EEG), brain injury, and long-term neurological outcome (e.g., epilepsy) remains controversial. The effects of hypoxia alone (Ha) and hypoxia-ischemia (HI) were studied in neonatal rats at postnatal day 7; both models generate EEG seizures during the 2-h hypoxia treatment, but only HI causes an infarct with severe neuronal degeneration. Single-channel, differential recordings of acute EEG seizures and background suppression were recorded with a novel miniature telemetry device during the hypoxia treatment and analyzed quantitatively. The waveforms of electrographic seizures (and their behavioral correlates) appeared virtually identical in both models and were identified as discrete events with high power in the traditional delta (0.1-4 Hz) and/or alpha (8 -12 Hz) bands. Although the EEG patterns during seizures were similar in Ha-and HI-treated animals at the beginning of the hypoxic insult, Ha caused a more severe electrographic seizure profile than HI near the end. Analyses of power spectral density and seizure frequency profiles indicated that the electrographic seizures progressively increased during the 2-h Ha treatment, while HI led to a progressive decrease in the seizures with significant suppression of the EEG background. These data show that 1) the hypoxia component of these two models drives the seizures; 2) the seizures during Ha are substantially more robust than those during HI, possibly because ongoing neuronal damage blunts the electrographic activity; and 3) a progressive decrease in background EEG, rather than the presence of electrographic seizures, indicates neuronal degeneration during perinatal HI.EEG; hypoxia-ischemia; neonatal; stroke; seizure SEIZURES ARE RELATIVELY COMMON in neonates and are a potential harbinger of intractable epilepsy, cerebral palsy, cognitive deficits, and other negative neurological outcomes. Prolonged periods of hypoxia alone (Ha; e.g., birth asphyxia or apnea) or hypoxia-ischemia (HI; e.g., perinatal stroke) are thought to be a major cause of neonatal seizures, but metabolic disturbances, encephalitis, and genetic abnormalities can also lead to seizures in neonates (Sarnat and Sarnat 1976;Finer et al. 1981; Watanabe et al. 1982a,b;Corey et al. 1988;Mercuri et al. 1999;Marin-Padilla 2000;Nelson and Lynch 2004;Malm 2009;Sorge and Sorge 2010). Although considerable EEG data are available on neonatal seizures, their predictive value is poor because outcomes range from benign to devastating. A definitive causal link between the characteristics of the neonatal EEG and the subsequent neurological outcome is difficult to establish in humans. Thus it is unclear whether acute neonatal seizures ...

Pharmaco‐resistant Neonatal Seizures: Critical Mechanistic Insights from a Chemoconvulsant Model

“…A). This phenomenon has been previously reported in a similar animal model of continuous seizures over a 2h recording period (Zayachkivsky et al, ). Human EEGs also show a reduction in overall seizure power with treatment (Pan et al, ).…”

Neuronal Circuit Activity during Neonatal Hypoxic–Ischemic Seizures in Mice

“…We observed that this rodent model of neonatal HI results in a characteristic pattern of behaviors consisting of both focal and multifocal seizures. Previous studies have also observed both focal and multifocal seizure semiology, 7,37,38 such as circling toward the ischemic side during neonatal rodent HI. [10][11][12] In conjunction, we observed clear asymmetries in the power spectrogram and cfos mapping of neuronal activity.…”

A physiologically-validated rat model of term birth asphyxia with seizure generation after, not during, brain hypoxia

“…Vannucci et al, 1995Vannucci et al, , 1997Vannucci et al, , 2001) simply mimic the effects of the endogenous hypercapnia, which are always associated with BA. In contrast to this, in current rodent models of BA and/or HIE which are based on exposure of rat and mouse pups to pure hypoxia induced by a gas mixture with a low O 2 (typically 4-8 % O 2 in N 2 ) (Greggio et al, 2009;Jensen et al, 1991;Rakhade et al, 2011;Rodriguez-Alvarez et al, 2015;Zanelli et al, 2014;Zayachkivsky et al, 2015), seizures are triggered already during the insult. Moreover, pure hypoxia (which does not occur under reallife physiological or pathophysiological conditions) evokes an immediate brain-confined alkalosis (Pospelov et al, 2020), which is exactly the opposite of what happens during asphyxia.…”