Journal
BIOLOGICAL RESEARCH
Volume 45, Issue 3, Pages 231-242Publisher
SOC BIOLGIA CHILE
DOI: 10.4067/S0716-97602012000300005
Keywords
hydrocephalus; abnormal neurogenesis; neural stem cells; stem cell transplantation
Categories
Funding
- Fondecyt [1070241, 1111018]
- Hydrocephalus Association Established Investigator Award
- Instituto de Salud Carlos III (Spain) [51002705, PS09/0376]
- Ministerio de Educacion y Ciencia (Spain) [PCI2006-A/-0669]
- Universidad Austral de Chile/DID [S-2006-72 to KV]
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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.
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