Altered Electroencephalography Spectral Profiles in Rats with Different Patterns of Experimental Brain Dysplasia.

Abstract

Malformations of cortical development, such as focal cortical dysplasia, are commonly associated with intractable epilepsy. Multiple animal models were created in attempts to recapitulate features of human malformations of cortical development. These manipulations give rise to various focal or diffuse anatomical abnormalities, accompanied by altered susceptibility to epileptic seizures. Both in humans and in models of dysplasia, the question of timing of the initiating insult is important. Here, we used a rat model of cerebral dysplasia elicited by prenatal irradiation at gestational days (E) 13, 15, 17, or 19. Previous results suggest these animals are characterized by different patterns of dysplasia as well as different reactivity to seizurogenic stimuli in several seizure models. Rats were implanted with telemetric electroencephalography (EEG) transmitters. We compared EEG data from freely moving animals with anatomical observations obtained with MRI, as well as Western blotting and immunohistochemistry. We performed spectral analyses of EEG signal, revealing differential regulation of specific bands (including delta, theta, alpha-beta, gamma) in animals with different patterns of dysplasia. Relative contribution of low-frequency activity in delta band is the lowest in E15 and the highest in E19. Conversely, higher frequency bands, corresponding to alpha/beta and gamma components, are reduced in E15 versus E19. This is accompanied by altered expression of glial markers in the E19 group. To our knowledge, this constitutes the first quantitative description of power spectral properties in this experimental model, providing insight into mechanisms underlying the anatomical and electrophysiological abnormalities associated with brain dysplasia of different types. Birth Defects Research, 110:303-316, 2018. © 2017 Wiley Periodicals, Inc.