Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke

Neuropharmacology. 2017 Apr;116:151-159. doi: 10.1016/j.neuropharm.2016.12.017. Epub 2016 Dec 21.

Abstract

Background: and purpose: Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS). Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke. The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS.

Methods: Middle Cerebral Artery Occlusion (MCAO) was achieved in neonatal Wistar rats by introducing a nylon filament to the left MCA for 3 h; 15 min after removing the occluder vehicle (MCAO-V) or CBD single dose 5 mg/kg (MCAO-C) were administered i. p. Similarly manipulated but non-occluded rats served as controls (SHM). A set of behavioral tests was then conducted one week (P15) or one month (P38) after MCAO. Brain damage was then assessed by magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (H+-MRS) and histologic (TUNEL for cell death, immunohistochemistry for neuron, astrocyte and microglia identification) studies.

Results: CBD administration improved neurobehavioral function regarding strength, hemiparesis, coordination and sensorimotor performance as assessed at P15 and P38. MRI indicated that CBD did not reduce the volume of infarct but reduced the volume of perilesional gliosis. H+-MRS indicated that CBD reduced metabolic derangement and excitotoxicty, and protected astrocyte function. Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation.

Conclusions: CBD administration after MCAO led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation.

Keywords: Cannabidiol; Neuroprotection; Newborn; Rats; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Astrocytes / physiology
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Ischemia / diagnostic imaging
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Cannabidiol / pharmacology*
  • Disease Models, Animal
  • Disease Progression
  • Microglia / drug effects
  • Microglia / pathology
  • Microglia / physiology
  • Motor Activity / drug effects
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Rats, Wistar
  • Recovery of Function / drug effects
  • Recovery of Function / physiology
  • Stroke / diagnostic imaging
  • Stroke / drug therapy*
  • Stroke / pathology
  • Stroke / physiopathology
  • Time Factors

Substances

  • Neuroprotective Agents
  • Cannabidiol