Mori Marco Aurélio, Meyer Erika, Soares Ligia Mendes, Milani Humberto, Guimarães Francisco Silveira, de Oliveira Rúbia Maria Weffort
Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
Department of Pharmacology, School of Medicine, USP, Av. Bandeirantes, 14015-000 Ribeirão Preto, São Paulo, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3;75:94-105. doi: 10.1016/j.pnpbp.2016.11.005. Epub 2016 Nov 23.
This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice. Using a multi-tiered behavioral testing battery during 21days, we found that BCCAO mice exhibited long-lasting functional deficits reflected by increase in anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like behavior (day 21). Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO. In addition, ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels. CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals. Collectively, the present results demonstrate that short-term CBD treatment results in global functional recovery in ischemic mice and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury.
本研究调查了大麻中存在的一种非致幻性植物化学物质大麻二酚(CBD)对小鼠双侧颈总动脉闭塞(BCCAO)所致认知和情感障碍的影响。在21天内使用多层行为测试组,我们发现BCCAO小鼠表现出长期的功能缺陷,表现为焦虑样行为增加(第9天)、记忆障碍(第12 - 18天)和绝望样行为(第21天)。短期给予10mg/kg的CBD治疗可预防认知和情感障碍,减轻海马神经变性和白质(WM)损伤,并减少BCCAO诱导的神经胶质反应。此外,用CBD治疗的缺血小鼠海马脑源性神经营养因子(BDNF)蛋白水平升高。CBD还刺激了神经发生,并促进了BCCAO动物海马中的树突重构。总体而言,目前的结果表明,短期CBD治疗可使缺血小鼠实现整体功能恢复,并影响脑缺血损伤病理生理学中多个不同的靶点。