Authors:
Pazos MR, Cinquina V, Gómez A, Layunta R, Santos M, Fernández-Ruiz J, Martínez-Orgado J.
Abstract:
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 < 0.05 vs. HV). CBD reduced brain infarct volume by 17%
(p < 0.05) and lessened the extent of histological damage. No
differences were observed between the SV and SC groups in any of the
experiments. In conclusion, CBD administration after HI injury to
newborn rats led to long-lasting neuroprotection, with the overall
effect of promoting greater functional rather than histological
recovery. These effects of CBD were not associated with any side
effects. These results emphasize the interest in CBD as a
neuroprotective agent for neonatal HI.