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

• Published in: Brain research 2010-11, Vol.1362, p.150-159
• Main Authors: Alonso-Alconada, Daniel, Alvarez, Francisco J, Alvarez, Antonia, Mielgo, Victoria E, Goñi-de-Cerio, Felipe, Rey-Santano, Maria C, Caballero, Amale, Martinez-Orgado, Jose, Hilario, Enrique
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Benzoxazines - pharmacology; Benzoxazines - therapeutic use; Biological and medical sciences; Brain damage; Calcium Channel Blockers - pharmacology; Calcium Channel Blockers - therapeutic use; Cannabinoid; Cannabinoid Receptor Modulators - pharmacology; Cannabinoid Receptor Modulators - therapeutic use; Disease Models, Animal; Female; Fetus; Hypoxia-Ischemia, Brain - drug therapy; Hypoxia–ischemia; Medical sciences; Morpholines - pharmacology; Morpholines - therapeutic use; Naphthalenes - pharmacology; Naphthalenes - therapeutic use; Neurology; Neuropharmacology; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Pharmacology. Drug treatments; Pregnancy; Pregnancy Complications - drug therapy; Psychodysleptics: hallucinogen; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Sheep, Domestic; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2010.09.050

Abstract 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.