Versatile strategies for adult neurogenesis: avenues to repair the injured brain

Abstract

Brain injuries due to trauma or stroke are major causes of adult death and disability. Unfortunately, few interventions are effective for post-injury repair of brain tissue. After a long debate on whether endogenous neurogenesis actually happens in the adult human brain, there is now substantial evidence to support its occurrence. Although neurogenesis is usually significantly stimulated by injury, the reparative potential of endogenous differentiation from neural stem/progenitor cells is usually insufficient. Alternatively, exogenous stem cell transplantation has shown promising results in animal models, but limitations such as poor long-term survival and inefficient neuronal differentiation make it still challenging for clinical use. Recently, a high focus was placed on glia-to-neuron conversion under single-factor regulation. Despite some inspiring results, the validity of this strategy is still controversial. In this review, we summarize historical findings and recent advances on neurogenesis strategies for neurorepair after brain injury. We also discuss their advantages and drawbacks, as to provide a comprehensive account of their potentials for further studies.

Keywords: adult neurogenesis; glia-to-neuron conversion; ischemic stroke; neurogenic niche; neuroinflammation; stem cell transplantation; traumatic brain injury.

Figure 1

Versatile strategies for post-injury neurogenesis. Although the presence of neurogenesis in the adult human brain is still controversial, injury-stimulated neurogenesis is anticipated to compensate for neuronal loss only to a limited extent. Although exogenous transplantation with mesenchymal, embryonic, neural, or induced-pluripotent stem cells is considered to alternatively enhance post-injury neurogenesis and has been evaluated in clinical trials, the impact of these approaches needs to be validated. Recent research further proposed that glial cells, including astrocytes, OPCs, and microglia, can potentially reprogram into neurons and replenish the neuronal population after brain injury, providing a novel avenue for brain injury therapy. Created with BioRender.com. ESC: Embryonic stem cell; iPSC: induced pluripotent stem cell; MSC: mesenchymal stem cell; NPC: neural progenitor cell; NSC: neural stem cell; OPC: oligodendrocyte precursor cell.