Increased seizure susceptibility of the immature brain

Moshé, Solomon L.; Albala, Bruce J.; Ackermann, Robert F.; Engel, J

doi:10.1016/0165-3806(83)90083-4

Cited by 213 publications

(52 citation statements)

References 14 publications

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“…The latencies to severe seizures measured at these two ages are considerably lower than those reported for adult Kv1.1 mice [Smart et al, 1998]. This early heightened susceptibility to seizures has been observed in immature rats [Moshé et al, 1983;Sperber and Moshé, 1988]. None of the P15 animals died following tonic extension, but a high mortality rate was observed following tonic extension at P24 for +/+ and +/-mice and at P30 for -/-and +/-mice ( fig.…”

Section: Seizure Susceptibility Is Dependent On Age and Genotypementioning

confidence: 62%

Developmental Seizure Susceptibility of Kv1.1 Potassium Channel Knockout Mice

Rho

Szot

Tempel³

et al. 1999

Dev Neurosci

109

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Potassium channels play a critical role in limiting neuronal excitability. Mutations in certain voltage-gated potassium channels have been associated with hyperexcitable phenotypes in both humans and animals. However, only recently have mutations in potassium channel genes (i.e. KCNQ2 and KCNQ3) been discovered in a human epilepsy, benign familial neonatal convulsions. Recently, it has been reported that mice lacking the voltage-gated Shaker-like potassium channel Kv1.1 α-subunit develop recurrent spontaneous seizures early in postnatal development. The clinical relevance of the Kv1.1 knockout mouse has been underscored by a recent report of epilepsy occurring in a family affected by mutations in the KCNA1 locus (the human homologue of Kv1.1) which typically cause episodic ataxia and myokymia. Here we summarize preliminary studies characterizing the developmental changes in seizure susceptibility and neuronal activation in the three genotypes of Kv1.1 mice (–/–, +/–, +/+). Using behavioral and immediate-early gene indicators of regional brain excitability, we have found that a seizure-sensitive predisposition exists in Kv1.1 –/– animals at a very young age (P10), before either spontaneous seizure activity or changes in c-fos mRNA expression can be demonstrated. Kv1.1 +/– mice, although behaviorally indistinguishable from wild types, also have an increased susceptibility to seizures at a similar early age. The Kv1.1 knockout mouse possesses many features desirable in a developmental animal epilepsy model and represents a clinically relevant model of early-onset epilepsies.

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Section: Seizure Susceptibility Is Dependent On Age and Genotypementioning

confidence: 62%

Developmental Seizure Susceptibility of Kv1.1 Potassium Channel Knockout Mice

Rho

Szot

Tempel³

et al. 1999

Dev Neurosci

109

View full text Add to dashboard Cite

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“…In contrast, there is a report that prenatal malnutrition may retard perforant path kindling in adult rats (15). Although the immature brain is more susceptible to seizures than the mature brain, several studies have demonstrated that a single bout of status epilepticus in immature rats, younger than 20 days old, results in less hippocampal cell loss, sprouting, and deficits in learning and memory than in adult rats (16)(17)(18)(19). Brief recurrent seizures in the early postnatal period can induce increased neurogenesis in the dentate gyrus (17), which is believed to play a role in increased epileptogenesis because of aberrant connections formed by these newly born dentate granule cells (20)(21)(22).…”

Section: S48mentioning

confidence: 89%

Malnutrition Increases Dentate Granule Cell Proliferation in Immature Rats After Status Epilepticus

et al. 2000

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Summary:Purpose: Nutritional insults early in life have a profound and often permanent effect on the development of the central nervous system. A direct relationship between malnutrition and epilepsy has not been established; however, it is believed that inadequate nutrition may predispose the brain to seizures. This study was designed to determine whether neonatally malnourished rats are different from nourished rats in terms of flurothyl seizure susceptibility at postnatal day (P)15, in the behavioral manifestations of seizures, and in status epilepticus-induced hippocampal injury.Methods: Sprague-Dawley rat pups were maintained on a starvation regimen from P2 until P17. Age-matched control rats were not exposed to starvation. At P15, all animals were exposed to flurothyl-induced status epilepticus. At P17, the rats received a single injection of bromodeoxyuridine (50 mg/kg intraperitoneal) to determine the extent of genesis of new cells in the dentate gyrus. At P18, the rats were killed, and the brains were processed for histology and immunohistochemistry.Results: Preliminary analysis indicates that early malnutrition did not modify flurothyl seizure susceptibility or the behavioral manifestations of seizures at P15. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. Malnutrition per se induced an increase in the genesis of new cells in the anterior dentate granule cell layer. Although exposure to status epilepticus augmented the expression of new cells in the dentate gyrus in both groups, this expression was more pronounced in the malnourished group.Conclusions: The findings suggest that malnutrition early in life alters dentate plasticity but not the susceptibility to flurothy1 seizures. Although status epilepticus can increase the expression of new cells in the dentate gyrus in immature rats, malnutrition followed by status epilepticus further increases dentate granule cell proliferation. Key Words: EpilepsyMalnutrition-Plasticity-CNS development-Hippocampus-Dentate gyrus.Malnutrition is one of the most important health problems in developing and underdeveloped countries. Nutritional insults early in life have a profound and often permanent effect on the subsequent development of the central nervous system. Clinical studies indicate that malnourished children have more learning and behavioral problems than well-nourished children (1-3). In a cross-sectional study from a pediatric population residing in a governmental institution, there was a trend toward a greater number of epilepsy cases among malnourished children compared with controls (4). However, a direct relationship between malnutrition and epilepsy has not been established in clinical studies.Many animal studies suggest that malnutrition may have detrimental effects on the brain and predispose the A decrease in the number of dendritic spines of pyramidal neurons of lamina I11 or V of the anterior cingulate cortex and in the CA3 hippocampal region was also described (6,7). Furtherm...

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“…The age of 8-33 days corresponds to the human developmental stages of infancy and childhood, and rat pups typically reach puberty between ages 33 and 38 days (15). Several studies indicate a period of increased seizure susceptibility in rats in the third week of life (16,17).…”

Section: Figmentioning

confidence: 99%

Anticonvulsant Efficacy of Gabapentin on Kindling in the Immature Brain

2001

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Summary:The anticonvulsant and motor effects of gabapentin (GBP) were evaluated in rat pups aged 16-17 days. Fourteen-day-old rat pups received an implanted stimulating electrode in the amygdala unilaterally. Kindled seizures were produced on day 16 of life by repeatedly applying an electrical current stimulus to the amygdala electrode. Animals received kindling stimulation until they achieved three consecutive generalized convulsions. On day 17, rat pups received one of four doses of GBP 10, 25, 50, or 100 mg/kg. After receiving GBP, rat pups again received electrical stimulation to the amygdala electrode to determine the extent to which GBP prevented the kindled seizure. Anticonvulsant effects were found at doses as low as 10 mg/kg. A separate group of naïve rats received GBP to determine the motor effects of each treatment dose. Impaired motor performance, quantified as time on a balance beam, occurred at doses of Ն50 mg/kg. In summary, our data indicate that in immature rats, GBP exerts an anticonvulsant effect against kindled seizures at doses that do not significantly impair motor performance. Key Words: GabapentinKindling-Amygdala.Gabapentin (GBP) is a widely used anticonvulsant medication approved for use in the United States as an adjunctive treatment of partial seizures with or without secondary generalization in patients older than 12 years. There are studies documenting and characterizing the efficacy of GBP against focal epilepsy in adult humans (1) and in animal models of focal seizures (2,3, and C. Taylor, personal communication). By comparison, relatively few clinical studies (4-8) and only one laboratory study (9) examined the effects of GBP in children younger than 12 years or in developing rats, respectively. We undertook to study the effects of GBP in an animal model of childhood temporal lobe epilepsy. We have previously modeled childhood temporal lobe epilepsy using developing rats exposed to amygdala kindling by repetitive electrical stimulation (10-12).In adult rats, GBP is effective against kindled hippocampal or amygdala seizures. Doses of 10-25 mg/kg subcutaneously or intraperitoneally correspond approximately to the typical doses used in humans. At doses of Ն10-30 mg/kg, GBP prevented or attenuated seizure propagation and generalization, as measured by improvement in the behavioral seizure score (2, and C. Taylor, personal communication). Suppression of epileptic activity within the hippocampus was seen only at doses higher than the minimal dose required to suppress seizure propagation. Only at higher doses did GBP suppress kindled epileptic activity within the hippocampus in adult rats. GBP doses >30 mg/kg were necessary to shorten the afterdischarge in the hippocampus. A dose of 300 mg/kg was required to increase the afterdischarge threshold. To date, GBP has not been tested against kindled seizures in developing rats. In this study, we report the anticonvulsant effects of GBP against kindled seizures in P15-P17 rat pups. METHODSSprague-Dawley albino rat pups (Charles River Laborato...

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Increased seizure susceptibility of the immature brain

Cited by 213 publications

References 14 publications

Developmental Seizure Susceptibility of Kv1.1 Potassium Channel Knockout Mice

Developmental Seizure Susceptibility of Kv1.1 Potassium Channel Knockout Mice

Malnutrition Increases Dentate Granule Cell Proliferation in Immature Rats After Status Epilepticus

Anticonvulsant Efficacy of Gabapentin on Kindling in the Immature Brain

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