Maximizing motor recovery: ultrastructural and functional analysis of axonal fusion mediated by polyethylene glycol (PEG), methylene blue (MB), and cannabidiol (CBD) in nerve injury models.

• Grant number: 24/10580-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2025
• End date: April 30, 2028
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Bruno Henrique de Melo Lima
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

This project aims to explore the underlying mechanisms and therapeutic benefits of the innovative technique of axonal fusion mediated by polyethylene glycol and methylene blue, in conjunction with cannabidiol therapy, in the treatment of severe nerve injuries. These injuries are mimicked through the transection of ventral roots or the sciatic nerve in rats, corresponding to brachial plexus and peripheral nerve traumas, respectively. Divided into two main stages, the project will initially address the transection of the ventral roots with various interventions, such as end-to-end coaptation with biological glue, axonal fusion and crushing. This phase aims to evaluate VGLUT1+ synapses in the spinal cord parenchyma up to twelve weeks after the injury. The second stage focuses on sciatic nerve transection and CBD treatment using different approaches, integrating functional (CatWalk system), electrophysiological (neuromuscular action potential recording and nerve conduction velocity), morphological (immunohistochemistry and volumetric electron microscopy - serial block face analysis) and molecular (qRT-PCR of genes related to ion channels) analyses to assess the recovery of nerve functions. Specific objectives include developing the technique of axonal fusion of ventral roots, evaluating glutamatergic coverage (VGLUT1+) and the neuroprotective effect of CBD, investigating its influence on calcium channel modulation and nerve regeneration. The expected results will provide valuable data on the mechanisms of axonal fusion and the impact of CBD on neural repair.