Brain dysplasia evoked by gamma irradiation at different stages of prenatal development leads to different tonic and clonic seizure reactivity

et al. 2017

Birth Defects Research

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Section: Discussionmentioning

confidence: 72%

“…Previously, we have described anatomical and cytoarchitectonic abnormalities in adult rats gamma‐irradiated at different time points during gestation (Setkowicz et al, ). These anomalies, as seen in T2‐weighted MRI, can be classified into three different severities: mild, with small heterotopic nodules present in the ventricles (Fig.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2017

Birth Defects Research

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“…Immediately after injection, behavioral scoring of clonic pilocarpine‐induced seizures was carried out, based on a modified Racine scale and previously reported in our studies (for example, see: Setkowicz et al, ), as follows:…”

Section: Methodsmentioning

confidence: 99%

“…Notably, this increased excitatory cortical and hippocampal neurotransmission rarely translates into spontaneous seizures in the rat. Rather, the dysplastic animals are characterized by altered susceptibility to epileptogenic stimuli, such as the proconvulsant drugs pilocarpine and kainic acid (Setkowicz et al, ) or to electrical stimulation (Setkowicz et al, ). Notably, our previous studies in animals irradiated at different time points, corresponding to gestation days E13 to E19 (with the normal rat gestation taking around 22 days), have revealed different patterns of reactivity.…”

Section: Introductionmentioning

confidence: 99%

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Profiles of gene expression in the hippocampal formation of rats with experimentally‐induced brain dysplasia

Developmental Neurobiology

et al. 2018

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Malformations of cortical development (MCD) are a common cause of intractable seizures in humans. Among these, focal cortical dysplasia (FCD) poses an outstanding challenge. There are several subtypes of FCD that show significant variation in pathology and clinical presentation. All types exhibit disturbed cortical cytoarchitecture and increased propensity for seizures. The etiology is likely heterogenous, with mutations, specifically in genes related to mammalian target of rapamycin (mTOR), identified in only a subset of cases. A more complex mechanism, in which underlying genetic background interacts with early, pre- or perinatal injury or stress, has been proposed. Here, we used a well-established animal model of developmental malformations similar to MCD, induced by prenatal gamma irradiation. Previously, a significant variation between times of treatment has been shown, resulting in distinct and lasting patterns of dysplasia and differentially altered seizure propensity. We set out to describe the molecular background of these patterns by performing microarray analyses of hippocampal samples obtained from adult rats previously irradiated at distinct time points during gestation: E13, E15, E17 or E19 as well as controls. The analysis was performed in three conditions: naïve, during latent phase after pilocarpine-induced status epilepticus and after 21 days of transauricular electric shocks. A set of 22 transcripts, some with known functions related to brain development, epilepsy and reaction to injury, was found to be altered between these groups across all treatments. We discuss the functional implication of these molecular differences, in an attempt to provide broader temporal and developmental context. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 718-735, 2018.

Structural changes in the neocortex as correlates of variations in EEG spectra and seizure susceptibility in rat brains with different degrees of dysplasia

J of Comparative Neurology

et al. 2021

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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.