Comparison of the efficacy of 4-Hydroxy-TEMPO and Methylene Blue for the repair of damaged sciatic nerve and assessment of behavioral performance improvement with Neostigmine

• Grant number: 22/13353-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2023
• End date: August 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Lynn Ana Flavia Salamanca Guillen
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 18/05006-0 - Sensorimotor recovery following spinal root axotomy: use of different experimental approaches, AP.TEM

Abstract

Peripheral nerve damage is frequent and affects millions of patients each year, causing decreased or loss of sensory capacity, paralysis, or muscle weakness. After the damage, the Wallerian degeneration develops at the distal stump of the damaged nerve, progressing for days to weeks, so that the restoration is slow, and partial, which translates into a low recovery of sensorimotor function and muscular atrophy. In invertebrates, regeneration mechanisms are more efficient, since they can quickly and completely fuse damaged nerve endings. Studies have been conducted seeking to find peripheral nerve fusion protocols in mammals. Polyethylene glycol (PEG) can fuse the axonal ends of damaged peripheral nerves, generating faster recovery, and preventing Wallerian degeneration. Studies have shown that the application of the antioxidant methylene blue (MB) to the PEG fusion protocol improves the percentage of axonal and behavioral recovery. On the other hand, Tempol, a cyclic nitroxide with antioxidant capacity, has beneficial effects in animal models of spinal cord injury and has neuroprotective properties in damaged peripheral nerves, but has not been used for axon fusion. Thus, the present project seeks to compare the effectiveness of MB and Tempol for the repair of damaged peripheral nerves and to evaluate the beneficial potential of neostigmine, an acetylcholinesterase inhibitor, to improve the recovery of motor function. It is expected to find that Tempol has a better effect than MB in the axonal fusion process and that the use of neostigmine facilitates motor function after the fusion.