Arnold-Chiari-like malformation associated with a valproate model of spina bifida in the rat.
The brains of rat fetuses exposed to saline and valproic acid (VA: 600 mg/kg or 1,200 mg/kg) at 10 days of gestation were examined for structural changes similar to that seen for the Arnold-Chiari malformation (ACM) in humans. Only fetuses exposed to the 1,200-mg/kg level VA demonstrated spina bifida (SB) type widening of the vertebral arch when compared to saline treated animals. When compared to controls, both 600-and 1,200-mg/kg VA animals demonstrated microencephaly. The brains of treated animals demonstrated alterations in their angular morphology such that the cerebellum was displaced toward the foramen magnum in a manner akin to human ACM. These findings indicate that valproate-induced SB in the rat more closely approximates SB in humans than was previously appreciated and provides a model for experimental study of both SB and ACM.
Briner
W
W
Department of Psychology, University of Nebraska, Kearney 68849, USA.
Lieske
R
R
D000818:Animals; D001139:Arnold-Chiari Malformation / Q000139:chemically induced*; D001921:Brain / Q000002:abnormalities / Q000033:anatomy & histology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000196:embryology; D008098:Litter Size / Q000187:drug effects; D008159:Lumbar Vertebrae / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D051381:Rats; D012447:Sacrum / Q000033:anatomy & histology / Q000187:drug effects; D016135:Spinal Dysraphism / Q000139:chemically induced*; D013904:Thoracic Vertebrae / Q000033:anatomy & histology / Q000187:drug effects; D014635:Valproic Acid
D014635:Valproic Acid