title: The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors.
abstract: To investigate the mechanisms involved in cannabidiol (CBD)-induced neuroprotection in hypoxic-ischemic (HI) immature brain, forebrain slices from newborn mice underwent oxygen and glucose deprivation in the presence of vehicle, or CBD alone or with selective antagonists of cannabinoid CB(1) and CB(2), and adenosine A(1) and A(2) receptors. CBD reduced acute (LDH efflux to the incubation medium) and apoptotic (caspase-9 concentration in tissue) HI brain damage by reducing glutamate and IL-6 concentration, and TNFalpha, COX-2, and iNOS expression. CBD effects were reversed by the CB(2) antagonist AM630 and by the A(2A) antagonist SCH58261. The A(1A) antagonist DPCPX only counteracted the CBD reduction of glutamate release, while the CB(1) antagonist SR141716 did not modify any effect of CBD. In conclusion, CBD induces robust neuroprotection in immature brain, by acting on some of the major mechanisms underlying HI cell death; these effects are mediated by CB(2) and adenosine, mainly A(2A), receptors.
authors.affiliation: Laboratorio de Apoyo a la Investigación, Hospital Universitario Fundación Alcorcón, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Castillo
authors.forename: M R
authors.initials: MR
authors.lastname: Tolón
authors.forename: J
authors.initials: J
authors.lastname: Fernández-Ruiz
authors.forename: J
authors.initials: J
authors.lastname: Romero
authors.forename: J
authors.initials: J
authors.lastname: Martinez-Orgado
mesh_terms: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology* / Q000627:therapeutic use; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009924:Organ Culture Techniques; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D002185:Cannabidiol; D061945:Caspase Inhibitors; D020169:Caspases; D018698:Glutamic Acid; D018836:Inflammation Mediators; D015850:Interleukin-6; D018696:Neuroprotective Agents; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D018047:Receptors, Purinergic P1; D000093242:Interleukin-6 Inhibitors