Received: 20 April 2000 Revised: 27 September 2000 Published online: 22 February 2001 © Springer-Verlag 2001 Abstract Our study was conducted to compare structural changes of brain exposed to 500 mg/kg valproic acid sodium (VA) at 10 days of ges- tation and 2×600 mg/kg VA at 9 days of gestation for Chiari-like malfor- mation (CLM). Brains, each still in the cranium, were placed under the dissecting microscope in such a way that the midsagittal surface for angu- lar 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 manu- ally and by means of a computer. The vertebral arch distances follow- ing 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 differ- ent angular morphology or point- to-point distances from those in fe- tuses 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 gesta- tion than in controls, but the distanc- es 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; specifi- cally, spina bifida aperta was not produced in this group. These ana- lyses 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 malfor- mation (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. Keywords Neural tube defect · Chiari malformation · Valproic acid Child’s Nerv Syst (2001) 17:399–404 DOI 10.1007/s003810000417 ORIGINAL PAPER Soner Duru Süreyya Ceylan Savas Ceylan Comparative effects of valproic acid sodium for Chiari-like malformation at 9 and 10 days of gestation in the rat Introduction Herniations of the rhombencephalon or hindbrain through the foramen magnum were first categorized in 1891 by Chiari [11], who described four types of patho- logic changes. These were later termed the Chiari mal- formations (CM). CM type 2 is sometimes referred to as the Arnold-Chiari malformation, giving credit to Arnold for a single description in 1894 following an autopsy [11]. A more appropriate term is simply CM type 2. CM type 2 is a complex disorder that encompasses anomalies of virtually the entire neuraxis, to a variable ex- tent. Most prominent among these are caudal displacement of the cerebellar vermis and tonsils into the cervical canal; elongation, kinking, and caudal displacement of the lower brain stem below the foramen magnum; upward displace- ment of the superior cerebellum through a dysplastic, low- lying tentorial incisura; and small posterior fossa [15]. CM type 2 lesions are almost always associated with spina bifida aperta or meningomyelocele [15]. Transi- S. Duru ( ✉ ) Department of Neurosurgery, Kocaeli University Medical Faculty, 41900 Kocaeli, Turkey e-mail: dsoner@superonline.com Tel.: +90-262-3112838 Fax: +90-262-2335463 S. Ceylan Department of Histology and Embryology, Kocaeli University Medical Faculty, 41900 Kocaeli, Turkey S. Ceylan Department of Neurosurgery, Kocaeli University Medical Faculty, 41900 Kocaeli, Turkey S. Duru Kocaeli Universitesi Tip Fakultesi, Norosirurji Anabilim Dali, Derince, 41900 Kocaeli, Turkey