Stimulating Endogenous Regeneration
The secondary injury signaling cascades after TBI or stroke are vast and complicated. The cognitive, emotional, and motor function of TBI and stroke patients may decline after injury partially due to the continuous neural cell death from the secondary injury cascades. Nonetheless, within these signaling cascades recent studies have identified upregulation of certain injury-response cytokines and growth factors that actually stimulate proliferative and migratory potential of endogenous neural stem/progenitor cells (NPCs) located in the hippocampus and subventricular zone (Figure 2; See reviews (Garzon-Muvdi and Quinones-Hinojosa, 2009; Richardson et al., 2010)). Such observations have stimulated questions such as: Where are these endogenous repair signals originating? Are these signals stemming from inflammation, cell death, immune response and/or angiogenesis? And, how are injury signals propagated from the injury site to the neural stem cell niche? In the case of TBI, both astrocytes and endothelial cells (ECs) have been shown to generate the NPC chemotactic signal stromal cell-derived factor-1 alpha (Itoh et al., 2009), while macrophages, microglia, and reactive astrocytes secrete leukemia inhibitory factor that induces NPC proliferation and self-renewal (Banner et al., 1997). However, the interaction and propagation of the injury signals from the damaged tissue to the subventricular zone still remains largely unknown. Understanding the endogenous pro-regenerative and repair signals after injury may lead to more rationally designed tissue engineered approaches.
