Prenatal methotrexate-induced cortical malformations are associated with decreased seizure susceptibility
Velisek, L; Kabova, R; Veliskova, J
| HERO ID | 5012629 |
|---|---|
| In Press | No |
| Year | 1998 |
| Title | Prenatal methotrexate-induced cortical malformations are associated with decreased seizure susceptibility |
| Authors | Velisek, L; Kabova, R; Veliskova, J |
| Journal | Epilepsia |
| Volume | 39 |
| Issue | SUPPL. 6 |
| Page Numbers | 8 |
| Abstract | Rationale: Intractable seizure syndromes in children are often associated with brain anomalies. We introduce a new model of brain damage induced by prenatal administration of folic acid antagonist methotrexate (MTX), which interferes with DNA synthesis. Methods: Pregnant rat dams were injected with 5 mg/kg of MTX in saline on gestation day 15 (at the time of formation of the neocortex, hippocampus, and striatum). Control rats received equivalent volume of saline. On the day of birth (postnatal day 0; PN0), the offspring were weighed and tattooed. Weight gains were followed up to PN20. Brains were examined for morphology by using thionin stain and GAD67 immunohistochemistry. The animals were also tested for seizure susceptibility by using flurothyl (PN15, 30, and 60) or hippocampal kindling (PN15). Results: There were no differences in the maternal weight between saline- and MTX-treated rat dams. However, the weight gain of the MTX-exposed offspring was slower through PN0-16, but not at PN18-20, compared with saline-exposed offspring. In MTX-exposed rats, thionin-stained sections demonstrated irregularities in the neocortical layer II-III and IV-V boundaries. In PN15 rats, GAD67 immunostaining revealed clusters of GAD67-positive cells in the neocortex with stained processes radial to the neocortical surface. Moreover, the MTX-exposed rats were more resistant to the development of flurothyl and kindled seizures than were saline exposed controls. Conclusions: Prenatal exposure to MTX induced a consistent decrease in susceptibility to seizures. The data suggest that not all cortical malformations due to prenatal insults are epileptogenic. |
| Wosid | BCI:BCI199900024387 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |