Among antiepileptic drugs, valproic acid (VA) is a well known
   teratogenic agent. Although axial skeletal malformations (vertebral column) and limb defects have been described, its main target organ is neuroepithelium of neural tube. Therefore it seems that administration of VA during early pregnancy may affect on neural tube and adjacent tissues. The goal of present study was to determine whether there is a relationship between maternal valproic acid exposure and developmental changes during neural tube and notochord and their interactions.

For this reason, on 9^th day of gestation, wistar rats were treated with double dose of 600 mg/kg VA given once in the morning and another in the evening (in experimental group). The controls were received the same volume of normal saline by animal feeding. For teratological studies, fetuses were examined on 20^thday of gestation and histological study were carried out.

Our findings showed that in addition to some well known congenital malformations (such as axial skeletal defects and spina bifida) there was an abnormal cavitation in cervical and thoracic segments of spinal cord (syringomyelia) which was accompanied with a delay in determination of notochord at these levels. At these area, the syrinx (cyst) is lined by compact glial tissue. In this kind of abnormality there is an atrophy of gray and white matter in the neighboring of syrinx in the spinal cord.

These data revealed that, there is a strong association between    maternal VA administration and risk for severe spinal cord defect such as syringomyelia and the same pathological changes might occur in human.