The mammalian brain retains actively proliferating progenitor cells and quiescent stem cells in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. Normally, these cells generate new neurons that migrate 1) from the SVZ through the rostral migratory stream to the olfactory bulb and differentiate into interneurons and 2) from the SGZ to the granule cell layer of the dentate gyrus. Brain damage induces neurogenesis in various experimental paradigms and raises the possibility of cell replacement from endogenous neural stem cells. The difficulty with these studies is that most often neurogenesis is defined in terms of 5¿Bromodeoxyuridine (BrdU) incorporation and the differentiation of BrdU+ cells into neurons. In the context of injury, a progenitor response would not only have to include proliferation, but also survival, differentiation, migration and integration into damaged tissue to provide a therapeutic outlook for brain regeneration.
The immature brain responds uniquely to injury; there is increased plasticity and improved outcome and a greater capacity for neurogenesis than the adult brain. However, few studies have been done on the immature brain and surprisingly little is known about the contribution of progenitor pools in recovery from immature brain damage. An understanding of the immature environment that is more permissive and shows increased plasticity may provide crucial insight into the underlying mechanisms of the precursor response in the mature central nervous system (CNS).
The principal objective of this thesis was to understand the proliferation and migration dynamics of progenitor cells after damage to the developing brain and subsequent determination of whether these cells were able to mature and integrate into the damaged tissue. Mechanisms used by neural progenitor and stem cells for survival and migration were also investigated.
A model of neonatal rat excitotoxicity was u
© 2001-2024 Fundación Dialnet · Todos los derechos reservados