Comparative effects of valproic acid sodium for Chiari-like malformation at 9 and 10 days of gestation in the rat

Abstract.

Our study was conducted to compare structural changes of brain exposed to 500 mg/kg valproic acid sodium (VA) at 10 days of gestation and 2×600 mg/kg VA at 9 days of gestation for Chiari-like malformation (CLM). Brains, each still in the cranium, were placed under the dissecting microscope in such a way that the midsagittal surface for angular morphology was seen, and video images were recorded for both study groups. Distances and angles in each brain were then measured on video image photographs both manually and by means of a computer. The vertebral arch distances following exposure to 500 mg/kg VA at 10 days of gestation were measured. VA on day 9 of gestation group was not followed by significantly different angular morphology or point-to-point distances from those in fetuses exposed to saline. In contrast, the angle formed between the frontal pole and cerebellum at the pons is more -acute in animals treated with VA 500 mg/kg on day 10 of gestation than in controls, but the distances were not reduced. However, the group exposed to VA 500 mg/kg on day 10 of gestation appeared to have sustained only minimal effects on the vertebral arch distances; specifically, spina bifida aperta was not produced in this group. These analyses may indicate that the anterior neural tube is more sensitive to the mechanism of action by which VA produces neural tube defects (NTDs) than is the posterior neural tube. Also, we can conclude that in these rat models, experimental CLM does not correspond to the Chiari malformation (CM) type 2. An animal model has its own species specificity and teratogenic environment, and the embryopathogenesis of NTD in the experimental animal model may not be directly applicable to the human condition.