Effects of dipropylacetate on brain development

Díaz, Jaime; Wd, Shields

doi:10.1002/ana.410100510

Cited by 27 publications

(9 citation statements)

References 22 publications

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“…Phenytoin can cause permanent damage to the cerebellum and occasionally a more in sidious encephalopathy [11], Phénobarbital can cause neuronal deficits and decrease body and brain weights [12,13], Valproate can cause a decrease of brain weight [9]. CZP is a new, potent antiepileptic drug, but infor mation regarding its effects on brain devel opment and cognitive function in children is not available.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, CZP did not cause significant effects on body weight, entire brain weight, or re gional brain weight. It is suggested that CZP has less effect on body and brain weights than phénobarbital, phenytoin, and val proate [9,12,13], However, an apparent trend towards decreased weight in all three measured parameters appeared in the highdose group. The high dosage (0.5 mg/kg/ day), when used for 16 days in mice (n = 35),…”

Section: Of Thementioning

confidence: 91%

“…To perform the straight-alley water-maze test, a rectangular metal box (40 cm long, 10 cm wide and 20 cm high) according to Diaz and Shields [9] was used. Warm water was added to a depth of 15 cm.…”

Section: Straight-alley Water-maze Testmentioning

confidence: 99%

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Effect of Clonazepam on Brain Development of Mice

Wang¹,

Huang²

1990

Dev Pharmacol Ther

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Twenty-seven Kun-Ming white mice were divided randomly into three groups of 9 animals. One of these groups served as a control group. Clonazepam (CZP), 0.1 or 0.5 mg/kg/day, was administered by oral gavage for 22 days. The water-maze test was performed before giving CZP and 10 and 22 days later. The step-down test was performed on the 1st and the 2nd day after discontinuing CZP treatment to determine toxic effects on brain development and learning-memory function. Body weights and brain weight were also recorded. Brain development and learning-memory function, evaluated by water-maze and step-down tests, were not impaired by CZP. Although there was a trend toward lower weights in the higher-dose group, CZP treatment did not significantly affect either body weight or total or regional brain weight. The results of this study indicate that 4 weeks of treatment with CZP does not impair brain development and learning-memory function in baby mice.

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Section: Discussionmentioning

confidence: 99%

Section: Of Thementioning

confidence: 91%

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Effect of Clonazepam on Brain Development of Mice

Wang¹,

Huang²

1990

Dev Pharmacol Ther

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“…Long Evans rats exposed during the early postnatal period (P6-P12) to valproate (150mg/kg) were found to have sensory-motor gating abnormalities and impairments in fine motor performance [17], while Sprague Dawley rats exposed exposed from P6-P18 to 150mg/kg of valproate showed deficits in the development of social play [18]. Relevant to neural development, P4-P18 rats exposed to 75–200mg/kg of valproate were found to have a significant decrease in brain weight [19] and rats exposed to three days of 50 to 400mg/kg of valproate between the ages of P3 and P30 were found to have increased apoptotic cell death throughout the brain, suggesting wide spread loss of cells [20–22]. Together, these results provide compelling support for more in depth studies of the effects of valproate on postnatal brain development.…”

Section: Introductionmentioning

confidence: 99%

Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice

Bath

Pimentel

2017

Epilepsy & Behavior

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Valproic Acid (Valproate) has been used for over 30 years as a first line treatment for epilepsy. In recent years, prenatal exposure to valproate has been associated with teratogenic effects, limiting its use in women that are pregnant or of childbearing age. However, despite its potential detrimental effects on development, valproate continues to be prescribed at high rates in pediatric populations in some countries. Animal models allow us to test hypotheses regarding the potential effects of postnatal valproate exposure on neurobehavioral development, as well as identify potential mechanisms mediating observed effects. Here, we test the effect of early postnatal (P4-P11) valproate exposure (100mg/kg and 200mg/kg) on motor and affective development in two strains of mice, SVE129 and C57Bl/6N. We also assessed the effect of early valproate exposure on regional BDNF protein levels, a potential target of valproate, and mediator of neurodevelopmental outcomes. We found that early life valproate led to significant motor impairments in both SVE129 and C57Bl/6N mice. Both lines of mice showed significant delays in weight gain, as well as impairments in the righting reflex (P7–8), wire hang (P17), open field (P12 and P21), and rotarod (P25 and P45) tasks. Interestingly, some of the early locomotor effects were strain and dose dependent. We observed no effects of valproate on early markers of anxiety-like behavior. Importantly, early life valproate had significant effects on regional BDNF expression, leading to a near 50% decrease in BDNF levels in the cerebellum of both strains of mice, while not impacting hippocampus BDNF protein levels. These observations indicate that postnatal exposure to valproate may have significant, and region specific effects, on neural and behavioral development, with specific consequences for cerebellar development and motor function.

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“…The main indication for its use is in treatment of absence seizures although it has been used in a variety of seizure disorders, often in combination with other anticonvulsants. Although VPA, as a carboxylic acid, is structurally unrelated to other kinds of anticonvulsant drugs, prenatal exposure to it, like other prenatal anticonvulsant exposures, has been associated with congenital malformations in laboratory animals [Brown et al, 1980;Kao et al, 1981: Diaz andShields, 1981;Bruckner et al, 1983;Paulson et al, 19851. VPA is known to cross the human placenta and is present in higher concentration in the infant than in the mother [Dickinson et al, 1979;Nau et al, 19811. Single case reports of birth defects occurring in offspring of women taking VPA during pregnancy have been published since 1980 suggesting that VPA might have teratogenic properties in humans as well [Dalens et al, 1980;Gomez, 1981;Thomas and Buchanan, 1981;Clay et al, 1981;Stanley andChambers, 1982: Bailey et al, 1983;Blaw and Woody, 1983;Bantz, 1984: Garden et al, 1985Tein and MacGregor, 19851.…”

mentioning

confidence: 99%

Verification of the fetal valproate syndrome phenotype

et al. 1988

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We have evaluated 19 children who were exposed to valproic acid (VPA) in utero to look for manifestations of a fetal valproate syndrome (FVS), as proposed by Di Liberti et al. [1984]. We found no consistent alterations of pre- or postnatal growth with exposure to VPA monotherapy. Postnatal growth deficiency and microcephaly were present however, in two thirds of children exposed to VPA in combination with other anticonvulsants. Developmental delay or neurologic abnormality was found in 71% of those exposed to VPA monotherapy, and in 90% of those exposed to VPA and other anticonvulsants. Craniofacial anomalies, which can be seen with other anticonvulsant exposures, including midface hypoplasia, short nose with a broad and/or flat bridge, epicanthal folds, minor abnormalities of the ear, philtrum or lip, and micrognathia were also found in infants whose mothers used VPA. Prominent metopic ridge and outer orbital ridge deficiency or bifrontal narrowing and certain major anomalies such as tracheomalacia, talipes equinovarus (with intact spine) and lumbosacral meningomyelocele seem to be peculiar to infants with VPA exposure. Other defects such as urogenital anomalies, inguinal or umbilical hernias, and minor digital anomalies that are common to other prenatal anticonvulsant exposures are also occasionally found in those exposed to VPA. Heart defects have been found in infants exposed to nearly every class of anticonvulsant although the types of defects associated with maternal VPA use may be clarified when classified by pathogenetic mechanism. Our findings overall are in agreement with the report of Di Liberti et al. [1984].

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Effects of dipropylacetate on brain development

Cited by 27 publications

References 22 publications

Effect of Clonazepam on Brain Development of Mice

Effect of Clonazepam on Brain Development of Mice

Effect of early postnatal exposure to valproate on neurobehavioral development and regional BDNF expression in two strains of mice

Verification of the fetal valproate syndrome phenotype

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