title: The cannabinoid receptor agonist WIN 55,212-2 reduces the initial cerebral damage after hypoxic-ischemic injury in fetal lambs.
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 0.01μg/kg WIN 55,212-2 (HI+WIN group) or not (HI+VEH) after 60min of a hypoxic-ischemic event. All animals were managed on mechanical ventilation for 3h 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.
authors.affiliation: Department of Cell Biology and Histology, School of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alonso-Alconada
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Alvarez
authors.forename: Antonia
authors.initials: A
authors.lastname: Alvarez
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Mielgo
authors.forename: Felipe
authors.initials: F
authors.lastname: Goñi-de-Cerio
authors.forename: Maria C
authors.initials: MC
authors.lastname: Rey-Santano
authors.forename: Amale
authors.initials: A
authors.lastname: Caballero
authors.forename: Jose
authors.initials: J
authors.lastname: Martinez-Orgado
authors.forename: Enrique
authors.initials: E
authors.lastname: Hilario
mesh_terms: D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy*; D009025:Morpholines / Q000494:pharmacology* / Q000627:therapeutic use; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D034561:Sheep, Domestic
chemical_list: D048588:Benzoxazines; D002121:Calcium Channel Blockers; D063385:Cannabinoid Receptor Modulators; D009025:Morpholines; D009281:Naphthalenes; D018696:Neuroprotective Agents; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone