Morphogenesis of experimental encephalocele (cranioschisis occulta)

Abstract

The structural organization of experimentally induced encephaloceles has been studied with both light and electron microscopy to ascertain the nature and origin of this type of axial dysraphic disorder. Three different experimental models (vitamin A, sodium arsenate and clofibrate) have been used to induce encephaloceles in hamster embryos. Regardless of the teratogen used, the induced encephaloceles are morphologically similar types of defects. An encephalocele is necessarily accompanied by a defect in the cranial vault (cranioschisis occulta) which is considered to be the result of an incomplete or faulty closure of the membranous neurocranium at the level of the defect. In addition, the basichondrocranium of these affected embryos is shorter than normal and lordotic to the axis of the vertebral column. The shortness of the base of the skull in these experimental encephaloceles is considered to be the result of an early mesodermal insufficiency resulting in a reduction in the number of para-axial mesodermal cells. The experimental encephalocele consists of a herniated portion of the mesencephalic roof through the defect of the cranial vault. It is usually located in the mid-line and posterior to the pineal invagination. The present study has demonstrated a central zone, in all encephaloceles, in which the neuroectoderm is fenestrated, suggesting an incomplete or faulty closure of the neural tube at that level. The surface ectoderm and small amount of hypoplastic mesodermal tissue are closed above the neural tube defect. Through the gaps formed between the fenestrated lamina of neuroectodermal cells, neuronal processes (predominantly growing axons) and some glial elements escape and enter into the ventricular cavity (cerebral aqueduct). Through these gaps the neuronal and glial processes also come in contact with the collagen and the mesodermal tissue which surrounds the neural tube. These gaps represent, therefore, microscopic meningoceles. Growing neuronal and glial processes of the developing mesencephalic centers when they arrive at the central zone of the encephalocele, penetrate directly into the ventricle and the surrounding mesodermal tissue through these gaps. In view of these observations, a new hypothesis concerning the morphogenesis of encephaloceles is advanced in this study. This new hypothesis proposes that the encephalocele is only one component of a complex type of axial dysraphic disorder which also involves the formation of the membranous neurocranium (cranioschisis occulta) and of the base of the skull (short basichondrocranium). It also proposes that a primary mesodermal insufficiency which could explain all these developmental abnormalities is the fundamental defect in this type of axial dysraphic disorder. A primary mesodermal insufficiency (reduction of the number of available para-axial mesodermal cells) could result in: (a) longitudinal growth impairment of the affected region of the axial skeleton resulting in its shortness; (b) growth impairment of the formation and progressive elevation of the neural folds necessary for their apposition and eventual closure, resulting in complete or incomplete (faulty) closure of all or only some of its components; (c) growth impairment of the cephalic dorsal mesoderm resulting in complete (schisis) or partial (lacunae) failure of closure of the membranous neurocranium; and (d) growth impairment of somites resulting in segmental abnormalities. All of these developmental abnormalities are found and characterize the experimental encephaloceles studied here. The hypothesis further proposes that encephaloceles are not primary malformations of the nervous tissue (neural tube) as is generally believed, but secondary developmental defects resulting from an incomplete or faulty closure of the neuroectoderm of the neural folds caused by an insufficient amount of supporting mesodermal tissue which is primarily affected.