Neuroependymal denudation is in progress in full-term human foetal spina bifida aperta

In human spina bifida aperta (SBA), cerebral pathogenesis [hydrocephalus, Sylvius aqueduct (SA) stenosis and heterotopias] is poorly understood. In animal models, loss of ventricular lining (ependymal denudation) causes SA stenosis and hydrocephalus. We aimed to investigate whether ependymal denudation also takes place in human foetal SBA. Considering that ependymal denudation would be related to alterations in junction proteins, sections through SA of five SBA and six control foetuses (gestational ages ranged between 37 and 40 weeks) were immunostained for markers of ependyma (caveolin 1, βIV-tubulin, S100), junction proteins (N-cadherin, connexin-43, neural cell adhesion molecule (NCAM), blood vessels (Glut-1) and astrocytes [glial fibrillary acidic protein (GFAP)]. In control foetuses, ependymal denudation was absent. In SBA foetuses different stages of ependymal denudation were observed: (i) intact ependyma/neuroepithelium; (ii) imminent ependymal denudation (with abnormal subcellular location of junction proteins); (iii) ependymal denudation (with protrusion of neuropile into SA, formation of rosettes and macrophage invasion); (iv) astroglial reaction. It is suggested that abnormalities in the formation of gap and adherent junctions result in defective ependymal coupling, desynchronized ciliary beating and ependymal denudation, leading to hydrocephalus. The presence of various stages of ependymal denudation within the same full-term SBA foetuses suggests continuation of the process after birth.