Drug repositioning: diacerein as a new therapeutic approach in a mice model of sciatic nerve injury.

BACKGROUND: Peripheral nerve injuries negatively impact the quality of life of patients, with no effective treatment available that accelerates sensorimotor recovery and promotes functional improvement and pain relief. The aim of this study was to evaluate the effects of diacerein (DIA) in an experimental mice model of sciatic nerve crush. METHOD: In this study, male Swiss mice were used, randomly separated into six groups as follows: FO (false-operated + vehicle); FO + DIA (false-operated + diacerein 30 mg/kg); SNI (sciatic nerve injury + vehicle); SNI + DIA in doses of 3, 10 and 30 mg/kg (sciatic nerve injury + treatment with diacerein in doses of 3-30 mg/kg). DIA or vehicle was administered 24 h after the surgical procedure, intragastrically, twice a day. The lesion of the right sciatic nerve was generated by crush. RESULTS: We found that the treatment of animals with DIA accelerated sensorimotor recovery of the animal. In addition, animals in the sciatic nerve injury + vehicle (SNI) group showed hopelessness, anhedonia, and lack of well-being, which were significantly inhibited by DIA treatment. The SNI group showed a reduction in the diameters of nerve fibers, axons, and myelin sheaths, while DIA treatment recovered all these parameters. In addition, the treatment of animals with DIA prevented an increase the levels of interleukin (IL)-1ß and a reduction in the levels of the brain-derived growth factor (BDNF). CONCLUSIONS: Treatment with DIA reduces hypersensitivity and depression like behaviors in animals. Furthermore, DIA promotes functional recovery and regulates IL-1ß and BDNF concentrations.

Optimal Morphometric Characteristics of a Tubular Polymeric Scaffold to Promote Peripheral Nerve Regeneration: A Scoping Review.

Cellular behavior in nerve regeneration is affected by the architecture of the polymeric nerve guide conduits (NGCs); therefore, design features of polymeric NGCs are critical for neural tissue engineering. Hence, the purpose of this scoping review is to summarize the adequate quantitative/morphometric parameters of the characteristics of NGC that provide a supportive environment for nerve regeneration, enhancing the understanding of a previous study. 394 studies were found, of which 29 studies were selected. The selected studies revealed four morphometric characteristics for promoting nerve regeneration: wall thickness, fiber size, pore size, and porosity. An NGC with a wall thickness between 250-400 µm and porosity of 60-80%, with a small pore on the inner surface and a large pore on the outer surface, significantly favored nerve regeneration; resulting in an increase in nutrient permeability, retention of neurotrophic factors, and optimal mechanical properties. On the other hand, the superiority of electrospun fibers is described; however, the size of the fiber is controversial in the literature, obtaining optimal results in the range of 300 nm to 30 µm. The incorporation of these optimal morphometric characteristics will encourage nerve regeneration and help reduce the number of experimental studies as it will provide the initial morphometric parameters for the preparation of an NGC.

Main Morphological Characteristics of Tubular Polymeric Scaffolds to Promote Peripheral Nerve Regeneration-A Scoping Review.

The "nerve guide conduits" (NGC) used in nerve regeneration must mimic the natural environment for proper cell behavior. OBJECTIVE: To describe the main morphological characteristics of polymeric NGC to promote nerve regeneration. METHODS: A scoping review was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) criteria in the PubMed, Web of Science, Science Direct, and Scientific Electronic Library Online (SciELO) databases. Primary studies that considered/evaluated morphological characteristics of NGC to promote nerve regeneration were included. RESULT: A total of 704 studies were found, of which 52 were selected. The NGC main morphological characteristics found in the literature were: (I) NGC diameter affects the mechanical properties of the scaffold. (II) Wall thickness of NGC determines the exchange of nutrients, molecules, and neurotrophins between the internal and external environment; and influences the mechanical properties and biodegradation, similarly to NGC (III) porosity, (IV) pore size, and (V) pore distribution. The (VI) alignment of the NGC fibers influences the phenotype of cells involved in nerve regeneration. In addition, the (VII) thickness of the polymeric fiber influences neurite extension and orientation. CONCLUSIONS: An NGC should have its diameter adjusted to the nerve with wall thickness, porosity, pore size, and distribution of pores, to favor vascularization, permeability, and exchange of nutrients, and retention of neurotrophic factors, also favoring its mechanical properties and biodegradability.

Aligned electrospun nerve conduits with electrical activity as a strategy for peripheral nerve regeneration.

Peripheral nerve injuries affect the quality of life of people worldwide. Despite advances in materials and processing in recent decades, nerve repair remains a challenge. The autograft is considered the most effective nerve repair in cases of serious injuries in which direct suture is not applied. However, the autograft causes the loss of functionality of the donor site, and additionally, there is a limited availability of donor nerves. Nerve conduits emerge as an alternative to the autograft and nowadays some conduits are available for clinical use. Nevertheless, they still need to be optimized for better functional nerve response. This review proposes to analyze the use of aligned electrospun nerve conduits with electrical activity as a strategy to enhance a satisfactory nerve regeneration and functional recovery.