Figure 1. NPC functions during physiological and pathological conditions.

(A) In physiological (homeostatic) conditions, NPCs reside within 2 main neurogenic niches, the SVZ and the SGZ, and undergo neurogenesis to maintain specific CNS circuits in the OB and in the DG. Concurrently, NPCs might exert non-neurogenic functions, such as controlling microglial cell behavior, through secretion of VEGF, and phagocytosis of maturing neurons. A recently reported non-neurogenic SVZ NPC function is the ability to act as scaffolding cells for the proper migration of DCs patrolling the CNS, allowing DC trafficking from the ventricles toward cervical lymph nodes. (B) In maladaptive (stressful) conditions, such as those occurring during pathology/inflammation, NPCs might also exert neurogenic and non-neurogenic functions aimed at maintaining or reestablishing dysfunctional CNS circuits. Depending on the pathological process, neurogenic functions are finalized to generate new neurons capable of integrating into functional circuits, whereas non-neurogenic functions are mainly aimed at limiting and/or preventing tissue damage and promoting tissue recovery. Non-neurogenic tissue restoration operates via a bimodal mechanism of action. On the one hand, SVZ NPCs do sense and contrast danger signals in order to avoid harmful inflammatory reactions through the production of soluble factors, such as cannabinoids, endovanilloids, and growth factors. On the other hand, SVZ NPCs generate new astrocytes that stabilize the glial scar and the BBB and new oligodendrocytes that promote remyelination. AEA, arachidonoylethanolamide; CC, central canal; CNTF, ciliary neurotrophic factor; OEA, oleoyl ethanolamide; PEA, palmitoyl ethanolamide; SCI, spinal cord injury.