Cannabidiol administration after hypoxia–ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function

Cannabidiol (CBD) demonstrated short-term neuroprotective effects in the immature brain following hypoxia–ischemia (HI). We examined whether CBD neuroprotection is sustained over a prolonged period. Newborn Wistar rats underwent HI injury (10% oxygen for 120 min after left carotid artery electrocoagulation) and then received vehicle (HV, n = 22) or 1 mg/kg CBD (HC, n = 23). Sham animals were similarly treated (SV, n = 16 and SC, n = 16). The extent of brain damage was determined by magnetic resonance imaging, histological evaluation (neuropathological score, 0–5), magnetic resonance spectroscopy and Western blotting. Several neurobehavioral tests (RotaRod, cylinder rear test[CRT],and novel object recognition[NOR]) were carried out 30 days after HI (P37). CBD modulated brain excitotoxicity, oxidative stress and inflammation seven days after HI. We observed that HI led to long-lasting functional impairment, as observed in all neurobehavioral tests at P37, whereas the results of HC animals were similar to those of sham animals (all p