Neurogenesis occurs in discrete regions of the adult mammalian brain. Numerous studies have examined the Neural Progenitor Cells(NPC) in the dentate gyrus and in the lining of the lateral ventricles in the hope of finding suitable materials for cell replacement therapies. However, little attention has been paid to the proliferative populations found in the sub-cortical white matter. White matter progenitor cells(WMPC) largely give rise to oligodendrocytes in vivo, but have been shown to have potential to generate neurons. We have developed a transgenic method to label NPC and their progeny; this provides a unique opportunity to examine the origins of this poorly understood population as well as their neurogenic potential. The central hypothesis will be that WMPC descend from nestin-positive stem cells and give rise to new neurons following ischemia-hypoxia. This hypothesis will be tested in three aims.
Aim 1 will examine the lineage of WMPC to determine when they segregate from other nestin-positive progenitors.
Aim 2 will examine cells generated after stroke and determine whether WMPC can give rise to neurons.
Aim 3 will test a cell replacement strategy by injecting growth factors into the lateral ventricles of stroke animals.
