Ischemia-Induced Neural Stem/Progenitor Cells Within the Post-Stroke Cortex in Adult Brains

Stroke is one of the major causes of death and disability in developed countries. The central nervous system (CNS) is known for its limited reparative capacity, but several studies demonstrated that the CNS has some reparative potential and cerebral ischemia is followed by activation of endogenous neurogenesis (Nakatomi et al., 2002; Taguchi et al., 2004). It is well-known that new neurons are continuously generated in specific brain regions such as the subventricular zones (SVZ) (Alvarez-Buylla et al., 2002) and the subgranular zone within the dentate gyrus of the hippocampus (SGZ) (Kuhn et al., 1996). Although adult cerebral cortical neurogenesis remains controversial, accumulating evidence has shown that under pathological conditions, new neurons are generated in the adult mammalian cerebral cortex (Magavi et al., 2000; Jiang et al., 2001; Jin et al., 2006; Yang et al., 2007). This suggests that neural stem/progenitor cells (NSPCs) can be activated in the cortex by brain injury such as ischemic stroke. In support of this notion, we demonstrated that NSPCs develop in the poststroke area of the cortex in the adult murine (Nakagomi et al., 2009a; Nakagomi et al., 2009b; Nakano-Doi et al., 2010; Saino et al., 2010) and human brain (Nakayama et al., 2010), and we referred to these as ischemia/injury-induced NSPCs (iNSPCs). These cells express markers of NSPCs, such as nestin and Sox2. They also form neurospheres that have the capacity for self-renewal, and differentiate into electrophysiologically functional neurons, astrocytes, and myelin-producing oligodendrocytes (Nakagomi et al., 2009a; Nakagomi et al., 2009b; Nakano-Doi et al., 2010; Clausen et al., 2011). In addition, we demonstrated that iNSPCs originate, at least in part, from within the cerebral cortex, but not from SVZ cells (Nakagomi et al., 2009b). However, the detailed origin and identity of the iNSPCs remains unclear. In this chapter, we introduce the characterization and possible origin of iNSPCs based on our reports and recent viewpoint, and compare them to other previously reported types of CNS stem/progenitor cells, including SVZ astrocytes (Doetsch et al., 1999), ependymal cells (Moreno-Manzano et al., 2009), reactive astrocytes (Shimada et al., 2010), resident glia (Zawadzka et al., 2010), and oligodendrocyte precursor cells (OPCs) (Kondo et al., 2000). We also refer to the possible cortical neurogenesis by iNSPCs and to the therapeutic potential of iNSPC transplantation in stroke patients.