The cannabinoid receptor agonist WIN 55,212-2 reduces the initial cerebral damage after hypoxic–ischemic injury in fetal lambs

The aim of the present work was to evaluate in an early time point the effect of the cannabinoid agonist WIN 55,212-2 after hypoxic–ischemic (HI) brain injury induced by partial occlusion of the umbilical cord of premature fetal lambs. Lambs were assigned to three experimental groups: one SHAM group: non-injured animals, and two hypoxic–ischemic groups that received a dose of 0.01 μg/kg WIN 55,212-2 (HI + WIN group) or not (HI +VEH) after 60 min of a hypoxic–ischemic event. All animals were managed on mechanical ventilation for 3 h and then sacrificed. Brains were perfusion-fixed and different regions separated for regional cerebral blood flow measurement, apoptosis quantification by TUNEL method and S-100 protein analysis by flow cytometry. The number of apoptotic cells was lower in the HI + WIN group in all regions studied. Moreover, animals treated with the cannabinoid agonist showed higher values in the percentage of S-100 positive cells in all regions, except in the cortex. In both studies we obtained similar values between SHAM group and HI + WIN group. Our results suggest that the administration of the cannabinoid agonist WIN 55,212-2 after hypoxic–ischemic brain injury in preterm lambs decreases brain injury reducing the delayed cell death and glial damage.

Research Highlights
► Hypoxia–ischemia triggers delayed cell death and glial damage.
► Cannabinoid agonist WIN 55,212-2 reduces TUNEL and maintains S100B-protein positive cells.
► WIN decreases delayed cell death and glial damage, reducing brain injury.