**2.4 Stress and glioma cancer stem cells**

Neural stem cells (NSCs) are specific to the central nervous system and are multipotent able to generate neurons, astrocytes, and oligodendrocytes. Like other stem cells, they are selfrenewing, proliferative, and quiescent until needed. NSCs are common during human embryonic development but are reduced in number and sequestered to specific regions of adult brains. These tiny subpopulations of cells can be recognized by their CD133+ status. In recent years, there has been a new consensus that gliomas contain a glioma cancer stem cell (GCSC) population in addition to other precursor and differentiated cancer cells. Thus, gliomas can express both neuronal and glial markers. There is accumulating evidence that NSCs are key players in tumor initiation and progression along with angiogenesis and dissemination. Thus, their presence is starting to redefine how therapy outcomes are determined and understanding their role in tumor progression and therapy resistance may be pivotal in improving patient prognoses.

For years it was thought that humans were born with all the brain cells that they were ever going to have and that mitosis of neural and glial cells only occurred during early development. While most cells in the CNS do exit the cell cycle as terminally differentiated cells early in life, it has come to light that neurogenesis continues throughout life in small areas of the brain including the subventricular zone (Lois & Alvarez, 1993) and the dentate gyrus (Kuhn et al., 1996). These locations are home to NSCs that exhibit the normal stem cell markers and are capable of migration and multipotency. The existence of these NSCs that are normally present in the brain provides precedence for the idea of mutipotent cells in the CNS and gliomas. As gliomas are known to be highly heterogeneous tumors with cells from multiple neural lineages, cancerous neural stem cells could explain this finding. Poor prognosis has been linked to glioma tumor heterogeneity (Pallini et al., 2008), which could be the result of GCSCs.
