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Neuroprotective effects of N, N-dimethyltryptamine and FGF-2 after ventral root avulsion and reimplantation with a heterologous fibrin biopolymer

Grant number: 21/02754-9
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2022
Effective date (End): October 31, 2025
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Alexandre Leite Rodrigues de Oliveira
Grantee:Paola Andrea Caro Aponte
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


The injuries to the brachial plexus (BPI) are the worst of all those sustained by the peripheral nerves. Ventral root avulsion (VRA) is an experimental approach to study BPI, which induces death of the vast majority of the affected adult motoneurons, triggering a strong glial reaction as well as synaptic detachment. To overcome the degenerative effects of VRA, combinatorial approaches could result in a significative regenerative response. Thus, we will investigate neuroprotection elicited by the association of surgical and pharmacological techniques that includes the use of root reimplantation with aid of a fibrin sealant derived from snake venom (HFS) and fibroblastic growth factor 2 (FGF-2). In addition, we will probe the effect of Sigma-1 agonist: N, N-dimethyltryptamine (DMT), a drug with neuroprotective and immunomodulatory effects. To analyze our model, we will employ a multidisciplinary approach combining neuronal survival, synaptic stability, glial reactivity, and function motor recovery 12 weeks post-lesion. Furthermore, we will use qRT-PCR to assess gene expression of Sigma-1, INMT, and anti-inflammatory and pro-inflammatory cytokines: TGF-², IL-4, IL-13, IL1², IL-6, TNF-±. The clinical relevance of our study is given by providing BPI a treatment, as to date there is not an effective protocol to address such lesion. We expect that the association of pharmacological treatment with DMT and root reimplantation with aid of HFS and FGF-2 may promote neuroprotection, preservation, and recovery of motor function, which may, in turn, offer a new therapeutic alternative for patients with spinal cord injuries.

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