Epileptogenesis in immature rats following recurrent status epilepticus

Santos, Nuno M.S. dos; Arida, Ricardo Mário; Filho, Euclides Maurício Trindade; Priel, Margareth Rose; Cavalheiro, Ésper A.

doi:10.1016/s0165-0173(99)00089-2

Cited by 47 publications

(57 citation statements)

References 48 publications

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“…These changes could underlie the behavioral deficits and generalized epileptic discharges observed in adulthood (15,16). The most prominent changes observed were (a) altered intracortical microcircuitry development; (b) anticipated PV immunoreactivity in neocortical interneurons; (c) increased GAD-65 immunoreactivity; and (d) altered neocortical apoptotic process.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Cortical Development as a Consequence of Repetitive Pilocarpine‐induced Status Epilepticus in Rats

et al. 2005

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Summary: Purpose:The aim of the present study was to observe possible cortical abnormalities after repetitive pilocarpineinduced status epilepticus (SE) in rats during development.Methods: Wistar rats received intraperitoneal injection of pilocarpine hydrochloride 2% (380 mg/kg) at P7, P8, and P9. All experimental rats displayed SE after pilocarpine injections. Rats were killed at P10 and P35, and immunocytochemistry procedures were performed on 50-µm vibratome sections, by using antibodies against nonphosphorylated neurofilament (SMI-311), parvalbumin (PV), calbindin (CB), calretinin (CR), and glutamate decarboxylase (GAD-65). Selected sections were used for the TUNEL method and double-labeling experiments, with different mixtures of the same markers. Results:The major findings of the present work were (a) altered intracortical circuitry development; (b) anticipation of PV immunoreactivity in neocortical interneurons; (c) increased GAD-65 immunoreactivity; and (d) reduced neocortical apoptotic process.Conclusions: From these results, we suggest that previously healthy brain, without genetic abnormalities, might develop an "acquired" disruption of cortical development whose evolution reproduces some characteristics of the childhood epilepsies associated with cognitive impairment. Key Words: Immature brain-Early insult-Apoptosis-Neocortex-Interneurons.In humans, the incidence of seizures is higher in the first year of life and decreases until adulthood (1,2). Although most of the early-life seizures are inherently benign, symptomatic febrile or hypoxic seizures are present in the history of many patients with temporal lobe epilepsy (TLE) and are believed to be associated with an underlying progressive epileptogenic process (3). Despite increasing knowledge of basic epileptology, the role of early-life seizures in the development of TLE remains an open question.In rats, neonatal seizures induce a range of hippocampal changes, such as glia activation and cytokine increase (4), altered glutamate and γ -aminobutyric acid (GABA)(A)-receptor gene immunoreactivity (5), persistent changes in intrinsic properties of CA1 cells (6), long-term behavioral deficits (7), and reduced hippocampal neurogenesis (8). Nevertheless, several studies have shown that the immature brain is resistant to seizure-induced hippocampal neuronal cell loss (9-12) and synaptic reorganization (11,13,14). Despite hippocampal resistance to neuronal Address correspondence and reprint requests to Dr. A. V. Silva at Lab Neurologia Experimental UNIFESP-EPM, Rua Botucatú, 862, CEP 04023-900 São Paulo, SP, Brazil. E-mail: valotta.nexp@epm.br damage during early development, Santos and colleagues (15,16) recently demonstrated that multiple episodes of pilocarpine-induced status epilepticus (SE) in developing rats (P7-P9) led to progressive neocortical/hippocampal epileptiform activity, persistent in vitro hyperexcitability, increased hippocampal/thalamic apoptosis, and severe cognitive impairment in adulthood.In contrast to adult rats that develop hippocam...

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Section: Discussionmentioning

confidence: 99%

Disruption of Cortical Development as a Consequence of Repetitive Pilocarpine‐induced Status Epilepticus in Rats

et al. 2005

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“…While the immature brain appears to be less vulnerable to the adverse effects of prolonged seizures than the mature brain 13 , seizures in the early life can be associated with later cognitive and behavioral disturbances, even in the absence of overt structural neuronal damage [14][15][16] . Previous study of our laboratory showed that 3 consecutive episodes of long-lasting pilocarpine-induced SE in developing rats (P7-9) is not able to promote neuronal loss but induces important electrographic and cognitive changes during adulthood 17 . Similarly, subtle impairments in intellectual performance have been reported in many individuals with a history of seizures in early life 18 .…”

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confidence: 85%

“…Furthermore, retrospective studies indicate that adults with mesial temporal lobe epilepsy report a high incidence of childhood status epilepticus 29 . Previously, our laboratory showed that although most of the animals submitted to SE (P7-9) did not develop spontaneous seizures in adulthood, they presented learning impairment and significant changes in cortical recordings, with episodes of complex spiking activity 17 . here we demonstrate increased temporal radial glia after injury induced by SE and delayed in radial glia disappearance.…”

Section: Fig 2 Details Of Cortical Radial Glia and Blood Vessels [Amentioning

confidence: 99%

Nestin down-regulation of cortical radial glia is delayed in rats submitted to recurrent status epilepticus during early postnatal life

Scorza

Arida

Scorza

et al. 2009

Arq. Neuro-Psiquiatr.

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-Objective: Nestin is temporarily expressed in several tissues during development and it is replaced by other protein types during cell differentiation process. This unique property allows distinguishing between undifferentiated and differentiated cells. This study was delineated to analyze the temporal pattern of nestin expression in cortical radial glial cells of rats during normal development and of rats submitted to recurrent status epilepticus (SE) in early postnatal life (P). Method: Experimental rats were submitted to pilocarpineinduced SE on P7-9. The cortical temporal profile of nestin was studied by immunohistochemistry at multiple time points (P9, P10, P12, P16, P30 and P90). Results: We observed delayed nestin down-regulation in experimental rats of P9, P10, P12 and P16 groups. In addition, few radial glial cells were still present only in P21 experimental rats. Conclusion: Our results suggested that SE during early postnatal life alters normal maturation during a critical period of brain development.KEy WOrdS: nestin, pilocarpine, status epilepticus, development, radial glia. atraso no desaparecimento da nestina na glia radial cortical de ratos submetidos a recorrentes status epilepticus durante o desenvolvimento pós-natal precoce resumo -Objetivo: A nestina, temporariamente expressa em diversos tecidos durante o desenvolvimento, é substituída no processo de diferenciação celular, o que permite a distinção entre células diferenciadas e indiferenciadas. O objetivo deste estudo foi verificar o padrão temporal da expressão da nestina nas células da glia radial cortical de ratos durante o desenvolvimento normal e nos ratos submetidos a sucessivos status epilepticus (SE) no periodo pós-natal precoce (P). Método: Os animais foram submetidos ao SE induzido pela pilocarpina em P7-9. O perfil temporal da nestina foi estudado por imuno-histoquímica em P9, P10, P12, P16, P30 e P90. Resultados: Nos ratos experimentais, observamos atraso no desaparecimento da nestina nos grupos P9, P10, P12 e P16. Ainda, encontramos algumas glias radiais corticais apenas em P21 experimental. Conclusão: Nossos resultados sugerem que o SE durante o desenvolvimento pós-natal precoce altera o processo de maturação durante um periodo crítico do desenvolvimento encefálico.

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“…21 Epileptogenesis refers to the events by which the normal brain becomes capable of producing epileptic seizures, i.e., the process by which neural circuits are converted from normal excitability to hyperexcitability. 56 As enumerated by White, 21 an appropriate animal model of epileptogenesis should share characteristics with human epilepsy, including similar pathology, a latent period following initial insult, chronic hyperexcitability and spontaneous seizures. Manipulations that produce prolonged seizures (Status Epilepticus -SE) in experimental animals have proven to satisfy all these criteria 57 .…”

Section: Experimental Epilepsymentioning

confidence: 99%

Malnutrition and experimental epilepsy

Gomes

Oliveira

Castro

2011

J. epilepsy clin. neurophysiol.

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Introduction: Disturbances in intrauterine environment can have harmful effects on the fetus and pathological consequences persisting throughout adolescence and adulthood. Protein restriction during the prenatal period has a significant impact on growth and development of the central nervous system. Food restriction increases the risk of neurological disorders such as epilepsy. Objective: To relate the programming model by malnutrition and its implications in experimental epilepsy. Material and methods: There has been research papers published in the databases Medline, PubMed, CAPES journals, ScienceDirect and Scielo. The keywords selected for the study included epilepsy, Status Epilepticus, pilocarpine, malnutrition, programming. Results and discussion: Several studies in animal models or humans highlights the possible adverse effects of malnutrition at the onset of epileptic seizures. The vulnerability immunological, biochemical and electrolyte abnormalities and hypoglycemia may be the factors responsible for the intensification of the epileptogenic process in malnourished individuals. Conclusion: Malnutrition negatively changes the epileptogenic circuitry.

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Epileptogenesis in immature rats following recurrent status epilepticus

Cited by 47 publications

References 48 publications

Disruption of Cortical Development as a Consequence of Repetitive Pilocarpine‐induced Status Epilepticus in Rats

Disruption of Cortical Development as a Consequence of Repetitive Pilocarpine‐induced Status Epilepticus in Rats

Nestin down-regulation of cortical radial glia is delayed in rats submitted to recurrent status epilepticus during early postnatal life

Malnutrition and experimental epilepsy

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