Cannabidiol Reduces Brain Damage and Improves Functional Recovery After Acute Hypoxia-Ischemia in Newborn Pigs

Newborn piglets exposed to acute hypoxia-ischemia (HI) received iv. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 +/- 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 +/- 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100 beta protein and brain tissue percentage of TNF alpha(+) cells were all higher. In contrast, in HI + CBD, aEEG had recovered to 86 +/- 5%, MRS parameters increased, and the neurobehavioral score normalized (34.3 +/- 1.4 points). HI induced histological changes, and NSE and S100 beta concentration and TNFa(+) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements. (Pediatr Res 70: 272-277, 2011)