Child's Nerv Syst (1987) 3:334-341 R6NS © Springer-Verlag 1987 Originalpapers Neural tube defects Some remarks on the possible role of glycosaminoglycans in the genesis of the dysraphic state, the anomaly in the configuration of the posterior cranial fossa, and hydrocephalus Concezio Di Rocco 1 and Mario Rende 2 1Institute of Neurosurgery and 2 Institute of Anatomy, Universit/t Cattolica School of Medicine, Largo Gemelli, 1, 1-00168 Rome, Italy Abstract. Recent developments in the field of experimen- tally induced neural tube defects (NTD) indicate that specific substances, namely the glycosaminoglycans (GAGs) may play a role in the genesis of spinal malfor- mations. The authors report the results obtained by evalu- ating the GAGs in rat fetuses with NTD, secondary to the administration of Trypan Blue during pregnancy. A char- acteristic decrease in GAGs formation in the spinal and cranial structures as well as in the subependymal regions of the brain was found in the malformed fetuses. The authors hypothesize that this anomaly in GAGs formation is responsible for both the NTD and the associated mal- formations, namely hydrocephalus and hypoplasia of the posterior cranial fossa. Key words: Neural tube defects - Trypan Blue - Gly- cosaminoglycans - Hydrocephalus - Meningocelemyelo - Chiari malformation. In spite of the more refined techniques of experimental investigation and clinical research, the pathogenetic theories of neural tube defects (NTD) are still deeply influenced by the early pathogenetic interpretations, namely the hypothesis of the primary lack of fusion of the neural tube, and that of the secondary rupture of a previously fused neural tube. As most of the studies have focused on the problem of the spinal defect, the anomalies associated with the NTD, namely hydrocephalus and posterior cervical fossa hypo- plasia, have almost always been regarded as secondary to the spinal malformation and explained by postulating mechanical causes. The aim of the present paper is to describe some experimental findings which, in our opinion, allow inter- pretation of both NTD and the associated anomalies of ectodermic and mesodermic structures. Offprint requests to: C. Di Rocco Historical background The first anatomical description of spina bifida was given by Tulpius [58], who in 1652 recognized the pathological presence of a nervous mass between opened spinal arches, a condition which he defined "spina dorsi bifida." Morgagni [30] was the first, in 1761, to describe the correlation between hydrocephalus and spina bifida and to propose a unique pathogenetic mechanism to explain the association of these two conditions. He suggested that dysraphism could result from dilatation caused by fluid accumulation ('"hydrops cerebri et rnedullaris") and the consequent rupture of a previously closed neural tube. The "dropsy" theory and secondary rupture of the neural tube was still considered by Cleland in his paper ""Contribution of the study of spina bifida, encephalocele and anencephalus", published in 1883 [6], together with a second hypothesis, i.e., deficient closure of the canal of the cerebrospinal axis or its coverings. The latter theory had obviously been influenced by the studies of Saint-Hilaire [44] on the influence of environmental and genetic factors on the embryos' development, which some years later, in 1886, would lead F. von Recklinghausen to suggest ""a primary defect" of neurulation as the cause of the non- closure of the neural tube [39]. In this century, two main pathogenetic theories have been propounded. The first of these still considers the lack of fusion of the neural tube as the first step leading to spina bifida. Variations on this theory have been proposed by several authors. In fact, Dekaben [8] indicated that the primary defect lay in an "abnormal orientation and organization" of the cells of the neural folds. Recently, Linville et al. [23] drew attention to the cytoskeletal system, and especially the microtubule-micro- filament system, inhibition of which can disturb the normal elevation and apposition of the neural folds to form the neural groove and then the neural tube [16]. This hypothesis has been confirmed by several experimental reports and anatomopathological researches in human dysraphic fetuses, and it is one of the most widely accepted at the present time.