Development of cortical malformations in BCNU-treated rat, model of cortical dysplasia

Moroni, Ramona Frida; Cipelletti, Barbara; Inverardi, Francesca; Regondi, Maria Cristina; Spreafico, Roberto; Frassoni, Carolina

doi:10.1016/j.neuroscience.2010.11.061

Cited by 20 publications

(26 citation statements)

References 46 publications

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“…Contrary to what has been previously described, in which periventricular heterotopia were detected since P1 [11], here we identified periventricular heterotopia already during embryonic development and we traced back their origin at E18. The birth of periventricular heterotopia could be correlated to the disorganization of the VZ that we observed in the BCNU-treated rats.…”

Section: Discussioncontrasting

confidence: 95%

“…Nonetheless, the number of transfected embryos was sufficient to perform a good analysis of neuronal migration. Indeed, the efficiency of cell transfection in control rats was consistent with data reported in the literature [12,21,22], whereas that of the BCNU-treated rats was less so, probably due to cell death induced by drug administration [11]. The overall analysis of electroporated cell distribution during cortical development revealed that the most obvious alterations of neuronal migration of the BCNU-treated cortices were detectable since E21.…”

Section: Discussionsupporting

confidence: 86%

“…The main finding of this study concerns the ontogenesis of periventricular heterotopia, an additional feature revealed in the BCNU-treated rats during adulthood and development [9,10,11]. Contrary to what has been previously described, in which periventricular heterotopia were detected since P1 [11], here we identified periventricular heterotopia already during embryonic development and we traced back their origin at E18.…”

Section: Discussionmentioning

confidence: 40%

“…The expression analysis of some layer-specific markers during embryonic and postnatal development has strongly suggested defects in neuronal migration and a rudimentary laminar pattern of the periventricular nodule found in BCNU-exposed cortex [11]. In the present study, we provide new evaluations about the altered neurogenesis that underlies CD development in the BCNU-treated rats by means of in utero electroporation - an in vivo approach that enables long-term analyses of neuronal migration.…”

Section: Discussionmentioning

confidence: 78%

“…The cytological and histological alterations of this model have been widely investigated in both adult and developing animals by means of immunohistochemical markers recognizing interneurons or pyramidal neurons, by analyzing the expression pattern of an appropriate panel of cortical layer-specific genes and by using magnetic resonance imaging [9,10,11]. Changes in neocortical organization of BCNU-treated rats have been revealed since the embryonic stages, when the disorganization of the ventricular wall, the disruption of the radial and tangential fibers, and the defective organization of the CP and subplate can be observed [9,10,11]. …”

Section: Introductionmentioning

confidence: 99%

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Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Moroni¹,

Inverardi²,

Regondi³

et al. 2013

Dev Neurosci

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Derangements of cortical development can cause a wide spectrum of malformations, generally termed ‘cortical dysplasia' (CD), which are frequently associated with drug-resistant epilepsy and other neurological and mental disorders. 1,3-Bis-chloroethyl-nitrosurea (BCNU)-treated rats represent a model of CD due to the presence of histological alterations similar to those observed in human CD. BCNU is an alkylating agent that, administered at embryonic day 15 (E15), causes the loss of many cells destined to cortical layers; this results in cortical thinning but also in histological alterations imputable to migration defects, such as laminar disorganization and cortical and periventricular heterotopia. In the present study we investigated the genesis of heterotopia in BCNU-treated rats by labeling cortical ventricular zone (VZ) cells with a green fluorescent protein (GFP) expression vector by means of in utero electroporation. Here, we compared the migratory pattern and subsequent distribution of the GFP-labeled cells in the developing somatosensory cortex of control and BCNU-treated animals. To this aim, we investigated the expression of a panel of developmental marker genes which identified radial glia cells (Pax6), intermediate precursors cells (Tbr2), and postmitotic neurons destined to infragranular (Tbr1) or supragranular layers (Satb2). The VZ of BCNU-treated rats appeared disorganized since E18 and at E21 the embryos showed an altered migratory pattern: migration of superficial layers appeared delayed, with a number of migrating cells in the intermediate zone and some neurons destined to superficial layers arrested in the VZ, thus forming periventricular heterotopia. Moreover, neurons that reached their correct position did not extend their axons through the corpus callosum in the contralateral hemisphere as in the control, but toward the ipsilateral cingulated cortex. Our analysis sheds light on how a malformed cortex develops after a temporally discrete environmental insult.

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Section: Discussioncontrasting

confidence: 95%

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 40%

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Moroni¹,

Inverardi²,

Regondi³

et al. 2013

Dev Neurosci

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Axon Initial Segment Structural Plasticity is Involved in Seizure Susceptibility in a Rat Model of Cortical Dysplasia

et al. 2018

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Cortical dysplasia is the most common etiology of intractable epilepsy. Both excitability changes in cortical neurons and neural network reconstitution play a role in cortical dysplasia epileptogenesis. Recent research shows that the axon initial segment, a subcompartment of the neuron important to the shaping of action potentials, adjusts its position in response to changes in input, which contributes to neuronal excitability and local circuit balance. It is unknown whether axon initial segment plasticity occurs in neurons involved in seizure susceptibility in cortical dysplasia. Here, we developed a "Carmustine"- "pilocarpine" rat model of cortical dysplasia and show that it exhibits a lower seizure threshold, as indicated by behavior studies and electroencephalogram monitoring. Using immunofluorescence, we measured the axon initial segment positions of deep L5 somatosensory neurons and show that it is positioned closer to the soma after acute seizure, and that this displacement is sustained in the chronic phase. We then show that Nifedipine has a dose-dependent protective effect against axon initial segment displacement and increased seizure susceptibility. These findings further our understanding of the pathophysiology of seizures in cortical dysplasia and suggests Nifedipine as a potential therapeutic agent.

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Classification of advanced methods for evaluating neurotoxicity

Han

Woo

2021

Mol. Cell. Toxicol.

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Purpose of review As fields such as neurotoxicity evaluation and neuro-related drug research are increasing in popularity, there is a demand for the expansion of neurotoxicity research. Currently, neurotoxicity is assessed by measuring changes in weight and behavior. However, measurement of such changes does not allow the detection of subtle and inconspicuous neurotoxicity. In this review, methods for advancing neurotoxicity research are divided into molecule-, cell-, circuit-, and animal model-based methods, and the results of previous studies assessing neurotoxicity are provided and discussed. Recent findings In coming decades, cooperation between universities, national research institutes, industrial research institutes, governments, and the private sector will become necessary when identifying alternative methods for neurotoxicity evaluation, which is a current goal related to improving neurotoxicity assessment and an appropriate approach to neurotoxicity prediction. Many methods for measuring neurotoxicity in the field of neuroscience have recently been reported. This paper classifies the supplementary and complementary experimental measures for evaluating neurotoxicity.

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Development of cortical malformations in BCNU-treated rat, model of cortical dysplasia

Cited by 20 publications

References 46 publications

Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Genesis of Heterotopia in BCNU Model of Cortical Dysplasia, Detected by Means of in utero Electroporation

Axon Initial Segment Structural Plasticity is Involved in Seizure Susceptibility in a Rat Model of Cortical Dysplasia

Classification of advanced methods for evaluating neurotoxicity

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