ABSTRACT
Most cells of the developing mammalian brain derive from the ventricular (VZ) and the subventricular (SVZ) zones. The VZ is formed by the multipotent radial glia/neural stem cells (NSCs) while the SVZ harbors the rapidly proliferative neural precursor cells (NPCs). Evidence from human and animal models indicates that the common history of hydrocephalus and brain maldevelopment starts early in embryonic life with disruption of the VZ and SVZ. We propose that a "cell junction pathology" involving adherent and gap junctions is a final common outcome of a wide range of gene mutations resulting in proteins abnormally expressed by the VZ cells undergoing disruption. Disruption of the VZ during fetal development implies the loss of NSCs whereas VZ disruption during the perinatal period implies the loss of ependyma. The process of disruption occurs in specific regions of the ventricular system and at specific stages of brain development. This explains why only certain brain structures have an abnormal development, which in turn results in a specific neurological impairment of the newborn. Disruption of the VZ of the Sylvian aqueduct (SA) leads to aqueductal stenosis and hydrocephalus, while disruption of the VZ of telencephalon impairs neurogenesis. We are currently investigating whether grafting of NSCs/neurospheres from normal rats into the CSF of hydrocephalic mutants helps to diminish/repair the outcomes of VZ disruption.
Subject(s)
Animals , Humans , Rats , Hydrocephalus/therapy , Intercellular Junctions/pathology , Neural Stem Cells/pathology , Stem Cell Transplantation/methods , Cell Differentiation , Cell Proliferation , Cerebral Aqueduct/pathology , Cerebral Ventricles/embryology , Cerebral Ventricles/pathology , Hydrocephalus/pathology , Neurogenesis , Neural Stem Cells/transplantationABSTRACT
Los antiinflamatorios no esteroidales (AINES) son medicamentos de uso común en problemas músculo-esqueléticos y artríticos; su utilización está asociada a múltiples efectos colaterales, siendo los gastrointestinales los más frecuentes y graves (gastropatía pos AINEs), que a veces obligan a la suspensión del tratamiento. Los análogos de las prostaglandinas y los inhibidores de la boma de protones, que actúan mediante efecto citoprotector y antisecretorio en la mucosa gastrointestinal, han demostrado efectividad protectora como la gastropatía por AINEs en varios estudios por separado. Actualmente disponemos del análogo sintético de las prostaglandinas E1, el misoprostol y el inhibidor de la bomba de protones, Omeprazol.