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 0.01μg/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.
Alonso-Alconada
Daniel
D
Department of Cell Biology and Histology, School of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
Alvarez
Francisco J
FJ
Alvarez
Antonia
A
Mielgo
Victoria E
VE
Goñi-de-Cerio
Felipe
F
Rey-Santano
Maria C
MC
Caballero
Amale
A
Martinez-Orgado
Jose
J
Hilario
Enrique
E
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
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