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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.

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  • Authors+Show Affiliations

    ,

    Laboratorio de Apoyo a la Investigación, Hospital Universitario Fundación Alcorcón, Spain.

    , , ,

    Source

    Neurobiology of disease 37:2 2010 Feb pg 434-40

    MeSH

    Adenosine A1 Receptor Agonists
    Adenosine A1 Receptor Antagonists
    Adenosine A2 Receptor Agonists
    Adenosine A2 Receptor Antagonists
    Aging
    Animals
    Animals, Newborn
    Apoptosis
    Brain
    Cannabidiol
    Caspase Inhibitors
    Caspases
    Cytoprotection
    Disease Models, Animal
    Down-Regulation
    Glutamic Acid
    Hypoxia-Ischemia, Brain
    Inflammation Mediators
    Interleukin-6
    Mice
    Mice, Inbred C57BL
    Nerve Degeneration
    Neuroprotective Agents
    Organ Culture Techniques
    Purinergic P1 Receptor Agonists
    Purinergic P1 Receptor Antagonists
    Receptor, Adenosine A1
    Receptor, Adenosine A2A
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Receptors, Purinergic P1

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19900555

    Citation

    TY - JOUR T1 - 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. AU - Castillo,A, AU - Tolón,M R, AU - Fernández-Ruiz,J, AU - Romero,J, AU - Martinez-Orgado,J, Y1 - 2009/11/06/ PY - 2009/8/3/received PY - 2009/10/22/revised PY - 2009/10/26/accepted PY - 2009/11/6/aheadofprint PY - 2009/11/11/entrez PY - 2009/11/11/pubmed PY - 2010/6/16/medline SP - 434 EP - 40 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 37 IS - 2 N2 - 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. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/19900555/abstract/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_ L2 - http://linkinghub.elsevier.com/retrieve/pii/S0969-9961(09)00309-X ER -