Neuroprotective effect of memantine after compressive radicular axotomy

• Grant number: 21/05180-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2021
• Effective date (End): November 30, 2022
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Alexandre Leite Rodrigues de Oliveira
• Grantee: Arthur Ventura Martins Leão
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Compressive root lesions are characterized by changes in the spinal cord's nervous microenvironment. Among these changes, the excitotoxic effect caused by glutamate, gliosis, and the subsequent maladaptive plasticity events stand out. Glutamate is an excitatory neurotransmitter that activates, among others receptors, the NMDAr ionotropic receptor. In light of the findings of how excessive NMDAr stimulation leads to neural degeneration processes, the idea of treatment of nerve injury events with NMDAr antagonists is raised. Thus, since memantine is a non-competitive NMDAr antagonist, this research project aims to assess its neuroprotective potential in the events of neural plasticity in the circuits of the anterior spinal cord after compressive root axotomy. For this purpose, we will crush the ventral root of adult C57BL / 6J mice, divided into two groups in which one will be treated with memantine in appropriate doses after the surgical procedure and the other will not. At the end of the therapeutic period, a hemilaminectomy to expose the spinal cord will be performed, as well as the dissection of the lumbar intumescences and subsequent immunohistochemistry for synaptophysin (pre-synaptic vesicle mark), GFAP (astrocyte marker), IBA1 (microglia marker), as well as analysis of motoneuron survival. The protocols concerning the handling and use of animals were submitted to CEUA / IB / UNICAMP and they were approved, as well as in accordance with COBEA guidelines. We hope to find greater neuronal survival in the experimental group evidenced by higher motor neuron count, as well as synaptic preservation and reduced gliosis, shown in immunohistochemistry. (AU)