title: Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia.
abstract: 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.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Mori
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: Erika
authors.initials: E
authors.lastname: Meyer
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: Ligia Mendes
authors.initials: LM
authors.lastname: Soares
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil.
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
authors.affiliation: Department of Pharmacology, School of Medicine, USP, Av. Bandeirantes, 14015-000 Ribeirão Preto, São Paulo, Brazil.
authors.forename: Francisco Silveira
authors.initials: FS
authors.lastname: Guimarães
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, 87020-900 Maringá, Paraná, Brazil. Electronic address: rmmwoliveira@uem.br.
authors.forename: Rúbia Maria Weffort
authors.initials: RMW
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002545:Brain Ischemia / Q000150:complications*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology*; D005106:Exploratory Behavior / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects*; D009479:Neuropeptides / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects*; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D000893:Anti-Inflammatory Agents; D002135:Calcium-Binding Proteins; D000089622:Doublecortin Domain Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D002185:Cannabidiol
keywords: Bilateral common carotid arteries occlusion; Cannabidiol; Neuroplasticity; Neuroprotection; White matter