**1. Introduction**

In 1928 Santiago Ramón y Cajal penned what became the accepted view about neurons in the central nervous system*; "everything may die, nothing can be regenerated"*. He later exhibited his wisdom by adding; *"It's the job of science to rewrite, if possible, this cruel phrase"* [1]. Up until 20 years ago, the scientific literature had emphasized that neurogenesis only occurs during development with no new neurons generated in the adult mammalian brain. However, since the discovery of adult neurogenesis, an extensive literature has emerged supporting the constant generation of new neurons in two neurogenic regions of the adult brain: the subven‐ tricular zone around the lateral ventricles (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) [2].

The existence of adult neurogenesis gave hope for recovery and regeneration from the many different insults that can damage the brain. After stroke or traumatic brain injury (TBI), immediate massive necrosis occurs followed by a subsequent prolonged period of inflamma‐ tion and further neuronal death [3]. Although brain injury induces massive cell loss, it also induces an increase in proliferation of NSCs residing in the neurogenic niches [4]. The environment of the neurogenic niche in adult animals is exquisitely regulated, with a finelytuned balance of soluble and cell-intrinsic factors that regulate the many different processes that are critical to neurogenesis: cell survival, proliferation, differentiation, and migration [5]. Dramatic changes occur in this environment as a consequence of the injury. The careful regulation of neurogenesis is disrupted by the many different cellular, soluble and vascular signals detected by the different cell types in the SVZ and DG. This major environmental alteration leads to increased proliferation of progenitor cells for long periods after the acute injury, yet the ability of the neural progenitor cells to fully differentiate, migrate and integrate into the lesioned area is limited [6]. Understanding the signals that regulate adult neurogenesis

© 2013 Villapol et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Villapol et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

in the naïve and injured animals is key to ultimately being able to harness the potential of neuronal replacement and improve stem cell therapy.

There are many different factors important to regulation of neurogenesis, many of which are discussed in other chapters in this book. Here we will focus on the role of the transforming growth factor-β (TGF-β) superfamily and its associated signaling pathways in regulating neurogenesis after brain injury. Members of this family, including the bone morphogenetic proteins (BMPs), Activin, and TGF-β1, -β2 and -β3 have a profound influence on the neuro‐ genic process in naïve animals [7]. Many of these cytokines are induced by injury and play critical roles in many kinds of brain damage related processes around the lesion [3]. We and others recently started to accumulate data on their induction in the neurogenic niches after different types of injury. Here we will focus on the relevance of their induction in these specific brain regions, and the mechanisms through which they may influence the neurogenic response to injury. As there are significant differences between the behavior of cells contributing to neurogenesis during development and in the adult, we will restrict our analysis to that observed in adult animals after injury. Delineation of the specific role of members of the TGFβ superfamily in injury-induced neurogenesis may provide specific therapeutic targets for enhancing neurogenesis after trauma.
