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Disturbances of the early stages of neurogenesis lead to irreversible changes in the structure of the mature brain and its functional impairment, including increased excitability, which may be the basis for drug‐resistant epilepsy. The range of possible clinical symptoms is as wide as the different stages of disturbed neurogenesis may be. In this study, we used a quadruple model of brain dysplasia by comparing structural and functional disorders in animals whose neurogenesis was disturbed with a single dose of 1 Gy of gamma rays at one of the four stages of neurogenesis, that is, on days 13, 15, 17, or 19 of prenatal development. When reached adulthood, the prenatally irradiated rats received EEG teletransmitter implantation. Thereafter, pilocarpine was administered and significant differences in susceptibility to seizure behavioral symptoms were detected depending on the degree of brain dysplasia. Before, during, and after the seizures significant correlations were found between the density of parvalbumin‐immunopositive neurons located in the cerebral cortex and the intensity of behavioral seizure symptoms or increases in the power of particular EEG bands. Neurons expressing calretinin or NPY showed also dysplasia‐related increases without, however, correlations with parameters of seizure intensity. The results point to significant roles of parvalbumin‐expressing interneurons, and also to expression of NPY—an endogenous anticonvulsant and neuroprotectant reducing susceptibility to seizures and supporting neuronal survival. [ABSTRACT FROM AUTHOR]

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To determine whether brains irradiated at different stages of prenatal development also have different postnatal susceptibility to seizures evoked by pilocarpine. Methods: Pregnant Wistar rats were exposed to a single 1.0-Gy dose of gamma rays on gestation days 13, 15, 17, or 19 (E13, E15, E17, and E19, respectively). On postnatal day 60, their offspring received i.p. pilocarpine injections to evoke status epilepticus. Behavior of the animals was observed continuously for 6 h after the injection, and motor manifestations of seizure activity were rated, and survival times recorded. After 7-day survival, the animals were killed, and their brains were weighed. Results: The average brain weight of animals exposed to irradiation at earlier prenatal stages (E13 or E15) was significantly lower than that after irradiation on E17 or E19. However, effects of the irradiation on the susceptibility to pilocarpine-induced seizures were quite opposite. The intensity of status epilepticus evoked in rats irradiated on E13 or E15 was significantly lower than that in nonirradiated controls or in those irradiated on E17 or E19. Moreover, after irradiation on E13 or E15, survival of the animals was significantly higher in relation not only to other irradiated groups but also to the controls. Conclusions: The results suggest than the extent of neuronal deficit, even if relatively greater, cannot always lead to higher susceptibility of the dysplastic brain to seizures. Functional consequences of the deficit, even if its magnitude is relatively smaller but involving specific brain areas, appear to be critical for the epileptogenesis. [ABSTRACT FROM AUTHOR]

Highlights: [•] The first use of electroshocks to check seizure susceptibility in dysplastic brains. [•] Electroshocks reveal new differences in seizure reactivity between dysplastic brains. [•] Periventricular heterotopias occur exclusively after irradiation on E15 or E17. [•] Brain dysplasia evoked on E17 promotes tonic but suppresses clonic seizures. [•] Opposite correlations of tonic and clonic seizures with the same morphological change. [ABSTRACT FROM AUTHOR]

Disorders of neurogenesis at early developmental stages lead to irreversible structural and functional impairments of the brain. As further their consequences, increases in brain excitability and the development of drug-resistant epilepsy can frequently be observed in clinical cases. Mechanisms underlying these phenomena can also be examined on animal models of brain dysplasia. This study was conducted on rats with four degrees of brain dysplasia following exposure to gamma radiation on days 13, 15, 17, or 19 of prenatal development. When reached adulthood, the rats received electroencephalographic (EEG) transmitter implantation. Thereafter, pilocarpine was administered, and significant differences in susceptibility to seizures were detected depending on the degree of brain dysplasia. Before, during, and after the seizures, EEG was recorded in free moving animals. Additionally, the intensity of seizure behavioral symptoms was assessed. Strong and moderate correlations were found between the intensity of seizure behavioral symptoms, the power of particular EEG bands, and volumes of dysplastic brains and their regions. The data drew particular attention to correlations between variations in EEG spectra and changes in the midbrain and pons volumes. The results point to possible significant roles of these regions in the observed changes of susceptibility to seizures. Consequently, the frequently used experimental model was considered here not only as representing cases of cortical dysplasia but also of generalized, diffuse dysplasia of the whole brain. Unlabelled Image • Standard model of cortical dysplasia includes volume changes in the brain stem. • EEG spectra in dysplastic brains reflect patterns of seizure behavioral symptoms. • Volumetric changes of brain regions correlate differently with seizure susceptibility. [ABSTRACT FROM AUTHOR]