Neurochemical Research

, Volume 37, Issue 1, pp 161–170 | Cite as

The Cannabinoid WIN 55212-2 Mitigates Apoptosis and Mitochondrial Dysfunction After Hypoxia Ischemia

  • D. Alonso-Alconada
  • A. Álvarez
  • F. J. Álvarez
  • J. A. Martínez-Orgado
  • E. Hilario
Original Paper


Perinatal hypoxia–ischemia has significant mortality and morbidity due to there is still no specific treatment as a consequence of the complexities of hypoxic-ischemic pathophysiology. The aim of this work was to evaluate the effects of the cannabinoid agonist WIN 55212-2 on apoptotic cell death and mitochondrial dysfunction after perinatal asphyxia in fetal lambs. Animals were assigned to: one SHAM group and two hypoxic-ischemic groups that received a dose of 0.01 μg/kg WIN 55,212-2 (HI + WIN) or not (HI + VEH) after 60 min of partial occlusion of the umbilical cord, and sacrificed 3 h later. Different brain regions were separated for morphological studies, and the same territories were dissociated and analyzed by flow cytometry to quantify apoptosis, to determine mitochondrial integrity and transmembrane potential and to analyze intracellular calcium levels. Our results showed that WIN 55,212-2 reduced apoptotic cell death in all regions studied through the maintenance of mitochondrial integrity and functionality.


Hypoxia–Ischemia Brain Apoptosis Mitochondria Cannabinoids 



We are grateful to Prof. David Hallett for his careful review of the manuscript. This work was supported by grants from Fondo de Investigación Sanitaria of Spanish Ministry of Health (PS09/02326) and from the Basque Government (GCI-07/79, IT-287-07).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • D. Alonso-Alconada
    • 1
  • A. Álvarez
    • 1
  • F. J. Álvarez
    • 2
  • J. A. Martínez-Orgado
    • 3
  • E. Hilario
    • 1
  1. 1.Department of Cell Biology and Histology, School of Medicine and DentistryUniversity of the Basque CountryLeioaSpain
  2. 2.Research Unit on Experimental Perinatal PhysiopathologyHospital de CrucesBarakaldoSpain
  3. 3.Neonatology Unit, Department of PediatricsHosptial Universitario Puerta de HierroMajadahonda, MadridSpain

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