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

Brain Res. 2010 Nov 29;1362:150-9. doi: 10.1016/j.brainres.2010.09.050. Epub 2010 Sep 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazines / pharmacology*
  • Benzoxazines / therapeutic use
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use
  • Cannabinoid Receptor Modulators / pharmacology
  • Cannabinoid Receptor Modulators / therapeutic use
  • Disease Models, Animal
  • Female
  • Fetus
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Morpholines / pharmacology*
  • Morpholines / therapeutic use
  • Naphthalenes / pharmacology*
  • Naphthalenes / therapeutic use
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Sheep, Domestic


  • Benzoxazines
  • Calcium Channel Blockers
  • Cannabinoid Receptor Modulators
  • Morpholines
  • Naphthalenes
  • Neuroprotective Agents
  • Win 55212-2