(NMDA)-induced seizures in developing rats

Mareš, Pavel; Velı́šek, Libor

doi:10.1016/0165-3806(92)90178-y

Cited by 129 publications

(78 citation statements)

References 21 publications

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“…The clinical phenotype of infantile spasms can be modeled by the administration of NMDA to rat pups [103][104][105]. These NMDA-induced seizures resembled clinical spasms with onset of spasm-like activity in immature rats, occurrence of spasms in clusters, and an EEG which resembled hypsarhythmia.…”

Section: Infantile Spasmsmentioning

confidence: 99%

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Holmes¹,

Zhao²

2008

Pediatric Neurology

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Epilepsy is a chronic condition caused by an imbalance of normal excitatory and inhibitory forces in the brain. Antiepileptic drug therapy has been directed primarily toward reducing excitability through blockage of voltage-gated Na + or Ca 2+ channels, or increasing inhibition through enhancement of γ-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals, usually rodents. Maximal electrical shock, pentylenetetrazol, and kindling are typically used as non-mechanistic screens for antiseizure properties and the rotorod test for assessing acute toxicity. While antiseizure drug screening has been successful in bringing drugs to the market and improving our understanding of the pathophysiology of seizures, it should be emphasized that the vast majority of drug screening occurs in mature male rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be effective in chronic models of epilepsy. Seizure type, clinical and electroencephalographic phenotype, syndrome, and etiology are often quite different in children with epilepsy than adults. Despite these age-related unique features, drugs used in children are generally the same as used in adults. As awareness of the unique features of seizures during development increases, it is anticipated that more drug screening in the immature animal will occur.

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Section: Infantile Spasmsmentioning

confidence: 99%

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Holmes¹,

Zhao²

2008

Pediatric Neurology

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“…A useful approach is to focus on a single region or circuit and assess multiple developmental processes, such as neurogenesis, synaptogenesis, dendritic growth, and functional maturity across species (see table in Avishai-Eliner et al [37] for such comparison of rat, monkey, and human hippocampus). This approach enables studying the role of specific stages of maturation of a given brain region on the susceptibility to seizures and the generation of specific seizure types (38)(39)(40)(41)(42). Insight from non-human work has suggested that the child's limbic circuit is characterized by an overshoot of axons in some hippocampal pathways (43), and an accompanying overshoot of excitatory synapses and glutamate receptors (31,32).…”

Section: The Child's Brain and Age-specific Seizuresmentioning

confidence: 99%

The Brain, Seizures and Epilepsy Throughout Life: Understanding a Moving Target

Baram

2012

Epilepsy Curr

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The Scope of the Problem The incidence of seizures and of epilepsy varies throughout life, peaking in neonates and children and increasing again after the age of 50 (1-4). In addition to the quantitative measure of the incidence of seizures, the type of seizures (and of epilepsy syndromes) varies with age: for example, febrile seizures take place in infants and children (1, 5-7), whereas the incidence of post-stroke epilepsy increases in adults compared with children (1,3,8). What is the basis of these age-dependent variations? What are the age-specific properties of the brain that contribute to the probability of seizure generation and to the nature of the resulting seizure?A second, reciprocal aspect of the interaction of the age of the brain and seizures involves the effects of a seizure on the structure and function of neurons and neuronal networks. Here, again, clinical evidence suggests that the consequences of a seizure might vary with age. For example, the consequences of status epilepticus (SE) in young children seem to depend on the inciting etiology (9, 10), and, in general, mortality and cognitive outcomes are more favorable than in the adult and elderly individual (11)(12)(13)(14). In contrast, status epilepticus in adult and aging individuals can have major detrimental effects on cognitive function and even survival (14-16). What is the basis of these age-dependent variations? What are the age-specific properties of the brain that modulate the effects of seizures on neuronal integrity and function?These questions are of paramount clinical importance because they should provide clues for developing age-specific diagnostic tools, prognostic models, and intervention strategies. Thus, while the answers to these questions are not fully elucidated, the questions provide a framework for discussing the salient elements of the evolving interaction between the brain and seizures throughout life.The following paragraphs highlight a few of the many facts that influence age-specific seizures and the age-specific consequences of seizures. Because most of the direct information about seizures throughout the life-span often derives from animal models, these are discussed. The author regrets that this overview is not comprehensive and likely omits a number of important publications. Nonetheless, this review serves to illustrate crucial features of the topic. Age-Specific Brain Properties Influence Seizures That Are Generated During Each AgeWhereas brain development from embryonic life to senescence is a continuum, here it is divided into four stages: the neonatal, childhood, adulthood, and aging epochs. The Neonatal Brain and Age-Specific Neonatal SeizuresThe neonatal brain is in a stage of rapid flux from both structural and functional perspectives. Neurons are still being born, circuits are being formed, and synapses are being established (17,18). Synaptic currents are often slower (19), neurotransmitters play trophic roles (20), and circuits are not fully mature (21). These facts predict that seizures may propag...

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“…This model was originally induced with the injections administered from P12 to P18 [45]. This model is most likely a model of acute seizure with hyperflexion and tonic spasms of the entire body, but the animals return after awhile to normal behavior.…”

Section: The Nmda Modelmentioning

confidence: 99%

Novel Animal Models of Pediatric Epilepsy

et al. 2012

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When mimicking epileptic processes in a laboratory setting, it is important to understand the differences between experimental models of seizures and epilepsy. Because human epilepsy is defined by the appearance of multiple spontaneous recurrent seizures, the induction of a single acute seizure without recurrence does not constitute an adequate epilepsy model. Animal models of epilepsy might be useful for various tasks. They allow for the investigation of pathophysiological mechanisms of the disease, the evaluation, or the development of new antiepileptic treatments, and the study of the consequences of recurrent seizures and neurological and psychiatric comorbidities. Although clinical relevance is always an issue, the development of models of pediatric epilepsies is particularly challenging due to the existence of several key differences in the dynamics of human and rodent brain maturation. Another important consideration in modeling pediatric epilepsy is that "children are not little adults," and therefore a mere application of models of adult epilepsies to the immature specimens is irrelevant. Herein, we review the models of pediatric epilepsy. First, we illustrate the differences between models of pediatric epilepsy and models of the adulthood consequences of a precipitating insult in early life. Next, we focus on new animal models of specific forms of epilepsies that occur in the developing brain. We conclude by emphasizing the deficiencies in the existing animal models and the need for several new models.

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(NMDA)-induced seizures in developing rats

Cited by 129 publications

References 21 publications

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

The Brain, Seizures and Epilepsy Throughout Life: Understanding a Moving Target

Novel Animal Models of Pediatric Epilepsy

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