Linking traumatic brain injury, neural stem, and progenitor cells

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and results in over 10 million hospitalizations on average each year. Following TBI, a variety of cell types are affected by both the initial tissue deformation and a secondary cascade of damaging molecular events. Neural stem and progenitor cells (NSPCs) play an impactful role in clinical recovery of locomotion, learning and memory. Among many other effects, TBI disrupts adult neurogenesis and hinders processes vital to the maintenance of the healthy brain. In this chapter, the dynamics of NSPCs after TBI will be discussed. TBI triggers the activation of NSPCs in the sub-granular zone (SGZ) of the hippocampus and the sub-ventricular zone (SVZ) of the cerebral cortex. However, due to changes to intrinsic and extrinsic factors, TBI-induced neurogenesis results in newborn cell death, ineffective integration of surviving cells into the neural circuitry, and deficits in locomotion, learning and memory. Thus, a deep understanding of NSPC dynamics in the developing and adult brain is necessary to develop effective treatment options for TBI. NSPCs have also been highly investigated for regenerative potential in medical applications in TBI, stroke, spinal cord injury, and neurodegenerative disorders, e.g., Parkinson’s and Alzheimer’s disease. Prospective therapeutic approaches for TBI are targeted to alter NSPC activity by providing intrinsic or extrinsic molecular signals. Therapeutics such as neurotrophic/growth factors, small molecules, gene therapy, and cell therapy are designed to restore healthy adult neurogenesis. Through these avenues, neurogenesis may provide the key to unlocking regenerative potential of the NSPCs in the brain.