Model of infantile spasms induced by <i>N</i>‐methyl‐<scp>D</scp>‐aspartic acid in prenatally impaired brain

Velı́šek, Libor; Jehle, Kamran; Velı́šková, Jana

doi:10.1002/ana.21082

Cited by 130 publications

(151 citation statements)

References 41 publications

(58 reference statements)

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“…Induction of Fos by systemic administration of NMDA in those brain regions has also been reported by other investigators (Knapp et al, 2001;Velisek et al, 2007). Furthermore, induction of seizures with PTZ and electroshock induces a massive Fos response in the VMH and nucleus of the solitary tract (Kanter et al, 1996;Andre et al, 1998;Barton et al, 2001;Eells et al, 2004).…”

Section: Discussionsupporting

confidence: 76%

Seizure responses and induction of Fos by the NMDA Agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction

et al. 2008

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Effects of the direct NMDA agonist (tetrazol-5-yl)glycine (TZG) were examined in a genetic mouse model of reduced NMDA receptor function. In this model, expression of the NR1 subunit is reduced but not eliminated and the mice are therefore designated as NR1 hypomorphic. Previous work suggested that the reduced NR1 subunit expression produced a functional subsensitivity as judged by a blunted Fos induction response to a sub-seizure dose of TZG. In the present study seizure threshold doses of TZG were tested in the wild type and mutant mice. Surprisingly, there was no difference in the seizure sensitivity between the wild type mice and mice presumed to express very low levels of the NR1 subunit. An extensive neuroanatomical analysis of Fos induction was conducted after the threshold seizure doses of TZG. The results demonstrate that some brain regions of the NR1 -/-mice exhibit much lower Fos induction in comparison to the NR1 +/+ mice. These regions include hippocampus, amygdala, and cerebral cortical regions. However, in other regions, similar induction of Fos was observed in both genotypes in response to the NMDA agonist. Regions showing similar Fos induction in the NR1 +/+ and NR1 -/-mice include the lateral septum, nucleus of the solitary tract, and medial hypothalamic regions. The results suggest that the NMDA receptor hypofunction in the NR1 -/-mice is not global but regionally specific and that subcortical structures are responsible for the seizure-inducing effects of TZG.Section 3-Neurophysiology, Neuropharmacology and other forms of Intercellular Communication

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Section: Discussionsupporting

confidence: 76%

Seizure responses and induction of Fos by the NMDA Agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction

et al. 2008

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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%

“…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. Since prenatal administration of a glucocorticoid can impair brain hypothalamic-pituitary-adrenal function [108], the authors administered betamethasone to pregnant rats.…”

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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“…On the other hand, if the pups are prenatally exposed to betamethasone or restraint stress on gestational day 15, injection of NMDA on postnatal day 10-15 triggers spasm-like seizures significantly earlier and in greater numbers [14][15][16]. "Pre-treatment" with repetitive ACTH injections decreases the number of seizures and improves the mortality [15,16].…”

Section: Experimental Models Of Ismentioning

confidence: 99%

Getting rid of the catastrophe: frontier research in infantile spasms

Ono

Galanopoulou

Moshé

2013

E&S

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Model of infantile spasms induced by N‐methyl‐D‐aspartic acid in prenatally impaired brain

Abstract: Despite certain limitations, our new model correlates well with current infantile spasm hypotheses and opens an opportunity for development and testing of new effective drugs.

Cited by 130 publications

References 41 publications

Seizure responses and induction of Fos by the NMDA Agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction

Seizure responses and induction of Fos by the NMDA Agonist (tetrazol-5-yl)glycine in a genetic model of NMDA receptor hypofunction

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

Getting rid of the catastrophe: frontier research in infantile spasms

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