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Neuroprotective effects of cannabidiol in spinal neurons and dorsal root ganglion sensory neurons after sciatic nerve transection in neonatal rats: role of CB1 and CB2 receptors

Grant number: 12/22751-5
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2013
Effective date (End): February 05, 2017
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Alexandre Leite Rodrigues de Oliveira
Grantee:Matheus Perez
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


The nervous system is one of the most sensitive tissues of the organism and is subject to various pathological conditions, either by neurodegenerative diseases such as Parkinson's disease, amyotrophic lateral sclerosis and Alzheimer's disease, or by mechanical trauma. A lot of injuries can reach the nervous system both in neonatal and adult, wich can become more severe due to the limited regenerative capacity. Despite the neonate presents a better regenerative capacity than adults, it is also limited and thus can result in irreversible damage and disabling. In order to better understand the processes that occur in response to injury in both neonate and adult the nervous system, and thus provide basis for new therapies, several experimental models have been proposed, for example, transection or crush of peripheral nerve. Furthermore, the use of substances with neuroprotective properties has been studied in the process of regeneration and synaptic plasticity, with the aim to prevent neuronal death after injury to the nervous system. Accordingly, cannabidiol (CBD) emerged as a potential strategy for the treatment of injuries due to their antioxidant and neuroprotective effect. Recent studies relate the action mechanisms of CBD to cannabinoid receptors. Thus, these receptors, like the endocannabinoid system, become targets for further studies. The aims of the present study are to investigate the neuroprotective potential of cannabidiol and its possible action via cannabinoid receptors. To do so, will be used newborn Wistar rats, that will be divided into five groups: 1) sciatic nerve crush and cannabidiol treatment (CBD group), 2) sciatic nerve crush and placebo treatment (PB group), 3 ) sciatic nerve crush and CBD + CB1 receptor antagonist treatment (CBD + ant-CB1 group); 4) sciatic nerve crush CBD + CB2 receptor antagonist treatment (CBD + ant-CB2 group) and 5) sciatic nerve crush with CBD + antagonist CB1 and CB2 receptors treatment (ant-CB1/CB2 + CBD group). To evaluate the expression of GFAP, Iba-1, synaptophysin, CB1 and CB2, we will use the technique of immunohistochemistry. To determine the survival of spinal motor and sensory neurons, we will use the Nissl staining and subsequent analysis by light microscopy. As for the assessment and quantification of gene expression on CB1, CB2, BDNF, GDNF and NGF, we use the RT-PCR technique in real time and to assess functional gait, we use the CATWALK system.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PEREZ, MATHEUS; CARTAROZZI, LUCIANA POLITTI; CHIAROTTO, GABRIELA BORTOLANCA; GUIMARAES, FRANCISCO SILVEIRA; DE OLIVEIRA, ALEXANDRE LEITE RODRIGUES. Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy. Neuropharmacology, v. 197, . (12/22751-5, 18/05006-0, 19/02714-7)
PEREZ, MATHEUS; CARTAROZZI, LUCIANA POLITTI; CHIAROTTO, GABRIELA BORTOLANCA; DE OLIVEIRA, SIMONE ALVES; GUIMARAES, FRANCISCO SILVEIRA; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE. Neuronal preservation and reactive gliosis attenuation following neonatal sciatic nerve axotomy by a fluorinated cannabidiol derivative. Neuropharmacology, v. 140, p. 201-208, . (12/22751-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
PEREZ, Matheus. Neuroprotective effects of cannabidiol in spinal motoneurons and dorsal root ganglion sensory neurons after sciatic nerve crush in neonatal rats: role of CB 1 and CB 2 receptors. 2018. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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