Transforming growth factor-β (TGF-β) belongs to a group of pleiotropic cytokines that are involved in a variety of biological processes, such as inflammation and immune reactions, cellular phenotype transition, extracellular matrix (ECM) deposition, and epithelial–mesenchymal transition. TGF-β is widely distributed throughout the body, including the nervous system. Following injury to the nervous system, TGF-β regulates the behavior of neurons and glial cells and thus mediates the regenerative process. In the current article, we reviewed the production, activation, as well as the signaling pathway of TGF-β. We also described altered expression patterns of TGF-β in the nervous system after nerve injury and the regulatory effects of TGF-β on nerve repair and regeneration in many aspects, including inflammation and immune response, phenotypic modulation of neural cells, neurite outgrowth, scar formation, and modulation of neurotrophic factors. The diverse biological actions of TGF-β suggest that it may become a potential therapeutic target for the treatment of nerve injury and regeneration.

Nerve injury is a common and difficult clinical problem worldwide with a high disability rate. Different from the central nervous system, the peripheral nervous system is able to regenerate after injury. Wallerian degeneration in the distal nerve stump contributes to the construction of a permissible microenvironment for peripheral nerve regeneration. To gain new molecular insights into Wallerian degeneration, this study aimed to identify differentially expressed genes and elucidate significantly involved pathways and cellular functions in the distal nerve stump following nerve injury. Microarray analysis showed that a few genes were differentially expressed at 0.5 and 1 hour post nerve injury and later on a relatively larger number of genes were up-regulated or down-regulated. Ingenuity pathway analysis indicated that inflammation and immune response, cytokine signaling, cellular growth and movement, as well as tissue development and function were significantly activated following sciatic nerve injury. Notably, a cellular function highly related to nerve regeneration, which is called Nervous System Development and Function, was continuously activated from 4 days until 4 weeks post injury. Our results may provide further understanding of Wallerian degeneration from a genetic perspective, thus aiding the development of potential therapies for peripheral nerve injury.

Peripheral nerves are composed of complex layered anatomical structures, including epineurium, perineurium, and endoneurium. Perineurium and endoneurium contain many physical barriers, including the blood-nerve barrier at endoneurial vessels and the perineurial barrier. These physical barriers help to eliminate flux penetration and thus contribute to the establishment of a stable microenvironment. In the current review, we introduce the anatomical compartments and physical barriers of peripheral nerves and then describe the cellular and molecular basis of peripheral physical barriers. We also specifically explore peripheral nerve injury-induced changes of peripheral physical barriers, including elevated endoneurial fluid pressure, increased leakage of tracer, decreased barrier-type endothelial cell ratio, and altered distributions and expressions of cellular junctional proteins. The understanding of the pathophysiological changes of physical barriers following peripheral nerve injury may provide a clue for the treatment of peripheral nerve injury.