Age‐Specific <i>N</i>‐Methyl‐D‐Aspartate—Induced Seizures: Perspectives for the West Syndrome Model

Kábová, Radka; Liptáková, Soña; Šlamberová, Romana; Pometlová, Marie; Velı́šek, Libor

doi:10.1111/j.1528-1157.1999.tb02006.x

Cited by 86 publications

(42 citation statements)

References 51 publications

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“…In addition, rats with NMDA-induced flexion seizures have impaired cognition when studied in adulthood [106]. However, the pharmacological response of the spasm-like behavior differed from children with infantile spasms in that the rats did not respond to glucocorticoids [103]. Recently, the model was altered by Velisek and colleagues [105], who reasoned that since infantile spasms may be secondary to disorders of the hypothalamic-pituitary-adrenal system [107], alteration of the adrenal brain axis may predispose the immature brain to spasms.…”

Section: Infantile Spasmsmentioning

confidence: 99%

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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%

“…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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“…These electroclinical characteristics fit human IS, even though interictal EEG cannot represent a true hypsarrhythmia. At the same time, the rats lose their righting reflex [44]. Cognitive deficits in the form of impairments in spatial learning and memory appear in adult rats following NMDA-induced seizures in pups [46].…”

Section: The Nmda Modelmentioning

confidence: 99%

“…The NMDA model is induced with intraperitoneal injections of the glutamate receptor agonist NMDA in rat pups between P10 and P15 [44]. This model was originally induced with the injections administered from P12 to P18 [45].…”

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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“…Another model of IS involves intraperitoneal injection of N-methyl-D-aspartate (NMDA) into rats on postnatal day 15 [10,11]. NMDA causes behavioral spasm-like seizure consisting of whole body tonic flexion with forward body-arching.…”

Section: Experimental Models Of Ismentioning

confidence: 99%