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The discovery of neural stem cells (NSCs) at the beginning of the nineties led many people to consider definitively broken the dogma of a static central nervous system (CNS) made up of non-renewable elements [1-3]. In parallel, the occurrence and characterization of adult neurogenesis in the olfactory bulb and hippocampus [3-5] triggered new hopes for brain repair. Twenty years after, the dream of regenerative medicine applied to brain/spinal cord injuries and neurodegenerative diseases is still very far [6,7]. As a matter of fact, adult neurogenesis in mammals occurs mainly within two restricted areas known as ‘neurogenic sites’ [3,8]: the forebrain subventricular zone (SVZ); reviewed in [9] and the hippocampal dentate gyrus (subgranular zone, SGZ); reviewed in [10]. As a direct consequence of such topographical localization, most of the CNS parenchyma out of the two ‘classic’ neurogenic sites remains substantially a non-renewable tissue. Actually, most of the traumatic/vascular injuries and neurodegenerative diseases do occur in ‘non-neurogenic’ regions and no efficacious therapies capable of restoring CNS structure and functions through cell replacement are at present available. Thus, two decades after the discovery of NSCs and the reaching of a satisfactory characterization of adult neurogenic sites, a gap remains between the occurrence of stem/ progenitor cells in the CNS of adult mammals and their effective capability to serve in brain repair. Several aspects do converge in explaining this gap [11], partially accounting for the heterogeneity of CNS structural plasticity in mammals (summarized in Table 1)

Parenchymal Neuro-Glio-Genesis Versus Germinal Layer- Derived Neurogenesis: Two Faces of Central Nervous System Structural Plasticity