Teratogenic valproic acid concentrations: Infusion by implanted minipumps vs conventional injection regimen in the mouse
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Cited by (138)
Toxicologic pathology of the reproductive system
2022, Reproductive and Developmental ToxicologyRole of Cbp, p300 and Akt in valproic acid induced neural tube defects in CD-1 mouse embryos
2020, Reproductive ToxicologyCitation Excerpt :Neural folds are formed at the edges of the neural plate which progress toward the midline and fuse to form the NT, the structure that subsequently develops into the brain and spinal cord [7]. One of the mechanisms resulting in neural tube defects is the failure of the NT to close at the midline, thus remaining open at any point between the cranial to caudal ends [8]. The incidence of NTDs, including anencephaly/exencephaly and lumbosacral meningomyelocele, is 1–2% in VPA-exposed human pregnancies [9].
Embryology and teratology
2019, The Laboratory RatValproic acid disrupts the biomechanics of late spinal neural tube closure in mouse embryos
2018, Mechanisms of DevelopmentCitation Excerpt :Evidence for this includes the distal spina bifida caused by in utero exposure to the anti-epileptic medication valproic acid (VPA) (Robert and Guibaud, 1982; Van Allen et al., 1993). In mice, exposure to VPA during neurulation also impairs NT closure, but the resulting defects primarily affect the cranial region causing exencephaly (the developmental forerunner of anencephaly) (Nau, 1985; Nau and Loscher, 1986). These teratogenic effects are distinct from VPA's anti-epileptic properties as not all of its anti-epileptic metabolites and analogues cause exencephaly when injected into mice (Nau and Loscher, 1986).
Adverse effects of prenatal and early postnatal exposure to antiepileptic drugs: Validation from clinical and basic researches
2017, Brain and DevelopmentCitation Excerpt :As for structural anomalies within the central nervous system, prenatal exposure to VPA is known to induce neural tube defects [53], neuronal migration defects leading to the impairment of neocortical lamination [54], increased weight of the whole brain [55], increased density of prefrontal neocortical neurons [56], apoptosis in the developing embryonic cerebral wall [57], and reduced adult neuronogenesis in the hippocampi [58]. It is important to note that these previous observations may not represent the effects of prenatal exposure to VPA in humans, since VPA was administered to pregnant rodents at high-dose (generally 400–500 mg/kg/dose; approximately twice the median effective dose (ED50), see Table 1), in a single or in multiple injections during the middle phase of embryogenesis, that is, usually on embryonic day 11 (E11) or E12, despite the short half-life of VPA in rodents (1–2 h) [53]. Thus, in more recent analyses, VPA was administrated to pregnant rodents at lower dosages for longer periods so as to reproduce the in utero environment in human epileptic mothers taking VPA.