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Influence of CB1 and CB2 cannabinoid receptors on axonal regeneration after sciatic nerve crush in C57BL/6J mice

Grant number: 15/25902-2
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2016
Effective date (End): September 30, 2017
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Alexandre Leite Rodrigues de Oliveira
Grantee:Nicoli Benitez Cadiolli
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The peripheral nervous system has limited regenerative capacity, so that injuries lead to significant impact on life quality. Despite the existence of surgical treatment, peripheral nerve injury uncommonly reach full recovery. Therefore, new strategies that provide better functional recovery are necessary, for instance, through the administration of substances with neuroprotective properties, for example, the cannabidiol (CBD). CBD mechanism of action seems to be related to the activation of CB1 and CB2 cannabinoid receptors. In this sense, it has been shown that treatment with CBD after peripheral nerve injury is associated with decrease in astrogliosis and microglial reactivity. Furthermore, CBD administration after nerve crush injury has provided better functional recovery, that could be enhanced with co-administration of a CB1 receptor antagonist. However, evaluation of CB1/2 antagonists alone has not been carried out. Thus, the present study aims to evaluate the effect of CB1 and CB2 antagonist administration on nerve regeneration and functional recovery after unilateral crush injury to the sciatic nerve. For that, 6-8 weeks old male C57BL/6J mice will be divided into five experimental groups: non-injured (control group); treatment with vehicle; treatment with CB1 antagonist; treatment with CB2 antagonist and treatment with both antagonists. After injury, mice will receive daily doses of antagonists (i.p.) for 15 days. After 4 weeks or full recovery, they will be euthanized and the spinal cords and distal portion of sciatic nerve will be evaluated by immunohistochemistry using the following antibodies: anti-GAP-43, anti-S100, anti-VGLUT1, anti-CB1 and anti-CB2. The functional recovery will be assessed through the CatWalk® system.

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