| Description |
Perinatal hypoxic-ischemic (PHI) encephalopathy afflicts roughly 1-2 in every 1000 live births, predisposing affected infants to a higher probability of developing epilepsy, cerebral palsy, and other neurological disorders. In many forms of acquired epilepsy, including PHI, there is a seizure-free period of time between the injury and the onset of the first spontaneous recurrent seizure (SRS) termed the latent period. In animal models of PHI, we aim to better understand the mechanisms that lead to an epileptic network that occur during this latent period. Due to limitations in performing electrophysiological experiments in immature animals, this time period remains under-studied in the pediatric population. We start our study at the cellular level using immunohistochemistry and whole-cell patch clamp methods before moving to the whole brain level with magnetic resonance imaging and the electroencephalogram (EEG) to examine anatomical and physiological changes that precede the development of epilepsy. We find that immediately after injury, early cell loss results in a reduction in the amount of excitatory and inhibitory synaptic input to pyramidal cells within the peri-infarct region. However, this reduction is short term, as there is a rapid recovery in the synaptic inputs 2 weeks later without any identifiable increase in the number of cells. As the brain continues to develop, the cellular loss that occurs early on leads to atrophy, and sometimes complete loss of the cortex, hippocampus, and thalamus. Even with major cell loss, power spectral analysis of the EEG identified no obvious reduction or increase in the power of any of the various cortical rhythms (delta, theta, alpha, beta, and gamma). However, EEG analysis did reveal the earliest known time point at which seizures occur in this animal model, as well as a previously undescribed short-duration convulsive seizure. Our findings suggest that the mechanisms responsible for the development of SRSs begin immediately after injury and result in a variable and progressive latent period. |
