Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity

Autor(es)

Meyer, Erika ^[1] ; Bonato, Jessica Mendes ^[1] ; Mori, Marco Aurelio ^[1] ; Mattos, Bianca Andretto ^[1] ; Guimaraes, Francisco Silveira ^[2] ; Milani, Humberto ^[1] ; de Campos, Alline Cristina ^[2] ; Weffort de Oliveira, Rubia Maria ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Maringa, Dept Pharmacol & Therapeut, Av Colombo 5790, BR-87020900 Maringa, Parana - Brazil

^[2] Univ Sao Paulo, Dept Pharmacol, Sch Med, Av Bandeirantes, BR-14015000 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Molecular Neurobiology; v. 58, n. 10 JUL 2021.
• Citações Web of Science: 1

Resumo

Evidence for the clinical use of neuroprotective drugs for the treatment of cerebral ischemia (CI) is still greatly limited. Spatial/temporal disorientation and cognitive dysfunction are among the most prominent long-term sequelae of CI. Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa that exerts neuroprotective effects against experimental CI. The present study investigated possible neuroprotective mechanisms of action of CBD on spatial memory impairments that are caused by transient global cerebral ischemia (TGCI) in rats. Hippocampal synaptic plasticity is a fundamental mechanism of learning and memory. Thus, we also evaluated the impact of CBD on neuroplastic changes in the hippocampus after TGCI. Wistar rats were trained to learn an eight-arm aversive radial maze (AvRM) task and underwent either sham or TGCI surgery. The animals received vehicle or 10 mg/kg CBD (i.p.) 30 min before surgery, 3 h after surgery, and then once daily for 14 days. On days 7 and 14, we performed a retention memory test. Another group of rats that received the same pharmacological treatment was tested in the object location test (OLT). Brains were removed and processed to assess neuronal degeneration, synaptic protein levels, and dendritic remodeling in the hippocampus. Cannabidiol treatment attenuated ischemia-induced memory deficits. In rats that were subjected to TGCI, CBD attenuated hippocampal CA1 neurodegeneration and increased brain-derived neurotrophic factor levels. Additionally, CBD protected neurons against the deleterious effects of TGCI on dendritic spine number and the length of dendritic arborization. These results suggest that the neuroprotective effects of CBD against TGCI-induced memory impairments involve changes in synaptic plasticity in the hippocampus. (AU)

• Processo FAPESP: 17/24304-0 - Novas perspectivas no emprego de fármacos que modificam neurotransmissores atípicos no tratamento de transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático