Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy

Autor(es)

Perez, Matheus ^{[1, 2]} ; Cartarozzi, Luciana Politti ^[2] ; Chiarotto, Gabriela Bortolanca ^[2] ; Guimaraes, Francisco Silveira ^[3] ; de Oliveira, Alexandre Leite Rodrigues ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Av Bandeirantes 3900, BR-14040907 Ribeirao Preto, SP - Brazil

^[2] Univ Campinas UNICAMP, Lab Nerve Regenerat, Cidade Univ Zeferino Vaz, Rua Monteiro Lobato 255, BR-13083970 Campinas, SP - Brazil

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Av Bandeirantes 3900, BR-14040907 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuropharmacology; v. 197, OCT 1 2021.
• Citações Web of Science: 0

Resumo

Neonatal rat sciatic nerve crush mimics obstetric axonotmesis, leading to extensive loss of motor and sensory neurons. The present study aimed to investigate the neuroprotective potential of cannabidiol (CBD) and the role of cannabinoid receptors after sciatic nerve crush in neonatal rats. For that, two-day-old Wistar rats were used, organized into the following experimental groups: sciatic nerve crush plus CBD treatment (CBD), crush plus vehicle treatment (VE), crush + CBD + AM251 treatment (AM251 - CB1 inverse agonist), crush + CBD + AM630 treatment (AM630 - CB2 antagonist). Spinal motoneuron survival was evaluated by Nissl staining of the lumbar spinal cord, 5- and 56-days following injury. CBD treatment enhanced neuronal survival by similar to 54 % both 5 days and 8 weeks after injury. However, AM251 and AM630 treatment decreased neuronal rescue by 30 % when compared to the CBD group, suggesting that CBD acts partially through such pathways. However, in the long term, only the CB1 blockade reverted CBD positive results. Synaptic preservation was evaluated by anti-synaptophysin immunolabeling. Five days after the lesion, CBD treatment preserved similar to 35 % of synapses in the ventral horn, and such effect was partially reversed by CB1 inactivation. Additionally, CBD treatment reduced astroglial reaction both at 5 days (39 %, compared to VE) and 8 weeks (31 %, compared to VE) after lesion. The microglial response was acutely reduced by 62 % after CBD treatment. Overall, the results herein show that CBD is neuroprotective, increasing neuronal survival and reducing glial reaction after neonatal axotomy. Such effects require CB1 and CB2 receptors to be effective, in turn influencing neuroprotection, glial reactivity, and functional recovery. (AU)

• Processo FAPESP: 12/22751-5 - Efeito neuroprotetor do canabidiol em neurônios medulares e neurônios sensitivos do gânglio dorsal após esmagamento do nervo isquiático em ratos neonatos: papel dos receptores canabinóideos CB1 e CB2.
• Beneficiário: Matheus Perez
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/05006-0 - Recuperação sensório-motora após axotomia de raízes medulares: emprego de diferentes abordagens experimentais
• Beneficiário: Alexandre Leite Rodrigues de Oliveira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/02714-7 - Estudo do envolvimento de MHC I, TLR 2 e TLR 4 na plasticidade sináptica e recuperação funcional após esmagamento de raízes ventrais em camundongos
• Beneficiário: Luciana Politti Cartarozzi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado