Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia

Prog Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3;75:94-105. doi: 10.1016/j.pnpbp.2016.11.005. Epub 2016 Nov 23.

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.

Keywords: Bilateral common carotid arteries occlusion; Cannabidiol; Neuroplasticity; Neuroprotection; White matter.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Brain Ischemia / complications*
  • Calcium-Binding Proteins / metabolism
  • Cannabidiol / pharmacology*
  • Cannabidiol / therapeutic use*
  • Disease Models, Animal
  • Encephalitis / drug therapy*
  • Encephalitis / etiology*
  • Exploratory Behavior / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Male
  • Maze Learning / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Neuronal Plasticity / drug effects*
  • Neuropeptides / metabolism
  • Recognition, Psychology / drug effects
  • Recovery of Function / drug effects*
  • Swimming / psychology
  • Time Factors

Substances

  • Aif1 protein, mouse
  • Anti-Inflammatory Agents
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Neuropeptides
  • doublecortin protein
  • Cannabidiol