Effects of cannabinoid (CBD) on blood brain barrier permeability after brain injury in rats

Brain Res. 2021 Oct 1;1768:147586. doi: 10.1016/j.brainres.2021.147586. Epub 2021 Jul 18.


Cannabidiol is a natural herbal medicine known to protect the brain from traumatic brain injury (TBI). Here, a TBI rat model was established, with cannabidiol administered intraperitoneally at doses of 5, 10, or 20 mg/kg, 30 min before surgery and 6 h after surgery until sacrifice. Brain water content, body weight, and modified neurological severity scores were determined, and enzyme-linked immunosorbent assay, immunofluorescence staining, hematoxylin and eosin staining, Nissl staining, Evans-blue dye extravasation, and western blotting were performed. Results showed that cannabidiol decreased the number of aquaporin-4-positive and glial fibrillary acidic protein-positive cells. Cannabidiol also significantly reduced the protein levels of proinflammatory cytokines (TNF-α and IL-1β) and significantly increased the expression of tight junction proteins (claudin-5 and occludin). Moreover, cannabidiol administration significantly mitigated water content in the brain after TBI and blood-brain barrier disruption and ameliorated the neurological deficit score after TBI. Cannabidiol administration improved the integrity and permeability of the blood-brain barrier and reduced edema in the brain after TBI.

Keywords: Blood brain barrier; Brain edema; Cannabidiol; Tight junction; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aquaporin 4 / metabolism
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Brain Edema / metabolism
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / metabolism
  • Cannabinoids / metabolism
  • Cannabinoids / pharmacology*
  • Claudin-5 / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Interleukin-1beta / metabolism
  • Male
  • Models, Animal
  • Neuroprotective Agents / pharmacology
  • Occludin / metabolism
  • Permeability / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism


  • Aquaporin 4
  • Cannabinoids
  • Claudin-5
  • Glial Fibrillary Acidic Protein
  • Interleukin-1beta
  • Neuroprotective Agents
  • Occludin
  • Tumor Necrosis Factor-alpha