Abstract

Objective

To identify circuits active during neonatal hypoxic‐ischemic (HI) seizures and seizure propagation using electroencephalography (EEG), behavior, and whole brain neuronal activity mapping.

Methods

Mice were exposed to hypoxia‐ischemia on postnatal day (p) 10 using unilateral carotid ligation and global hypoxia. EEG and video were recorded for the duration of the experiment. Using immediately early gene (IEG) reporter mice, active cells expressing cfos were permanently tagged with reporter protein, tdTomato, during a 90 minute window. After one week, allowing maximal expression of the reporter protein, whole brains were processed, lipid cleared, imaged with confocal microscopy. Whole brain reconstruction and analysis of active neurons (colocalized tdTomato/NeuN) was performed.

Results

HI resulted in seizure behaviors that were bilateral or unilateral tonic‐clonic and non‐convulsive in this model. Mice exhibited characteristic EEG background patterns, such as, burst suppression and suppression. Neuronal activity mapping revealed bilateral motor cortex and unilateral, ischemic somatosensory cortex, lateral thalamus, and hippocampal circuit activation. Immunohistochemical analysis revealed regional differences in myelination, which coincide with these activity patterns. Astrocytes and blood vessel endothelial cells also expressed cfos during HI.

Interpretation

Using a combination of EEG, seizure semiology analysis and whole brain neuronal activity mapping we suggest that this rodent model of neonatal hypoxia‐ischemia results in EEG patterns similar to those observed in human neonates. Activation patterns revealed in this study help explain complex seizure behaviors and EEG patterns observed in neonatal HI injury. This pattern may be, in part, secondary to regional differences in development in the neonatal brain.

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