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Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism.

Abstract

We examined the neuroprotective mechanism of cannabidiol, non-psychoactive component of marijuana, on the infarction in a 4 h mouse middle cerebral artery (MCA) occlusion model in comparison with Delta(9)-tetrahydrocannabinol (Delta(9)-THC). Release of glutamate in the cortex was measured at 2 h after MCA occlusion. Myeloperoxidase (MPO) and cerebral blood flow were measured at 1 h after reperfusion. In addition, infarct size and MPO were determined at 24 and 72 h after MCA occlusion. The neuroprotective effect of cannabidiol was not inhibited by either SR141716 or AM630. Both pre- and post-ischemic treatment with cannabidiol resulted in potent and long-lasting neuroprotection, whereas only pre-ischemic treatment with Delta(9)-THC reduced the infarction. Unlike Delta(9)-THC, cannabidiol did not affect the excess release of glutamate in the cortex after occlusion. Cannabidiol suppressed the decrease in cerebral blood flow by the failure of cerebral microcirculation after reperfusion and inhibited MPO activity in neutrophils. Furthermore, the number of MPO-immunopositive cells was reduced in the ipsilateral hemisphere in cannabidiol-treated group. Cannabidiol provides potent and long-lasting neuroprotection through an anti-inflammatory CB(1) receptor-independent mechanism, suggesting that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.

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  • Publisher Full Text
  • Authors

    Hayakawa K, Mishima K, Nozako M, Hazekawa M, Irie K, Fujioka M, Orito K, Abe K, Hasebe N, Egashira N, Iwasaki K, Fujiwara M

    Source

    Journal of neurochemistry 102:5 2007 Sep pg 1488-96

    MeSH

    Animals
    Behavior, Animal
    Cannabidiol
    Cerebrovascular Circulation
    Disease Models, Animal
    Dose-Response Relationship, Drug
    Dronabinol
    Functional Laterality
    Glutamic Acid
    Infarction, Middle Cerebral Artery
    Male
    Mice
    Motor Activity
    Neuroprotective Agents
    Perfusion
    Peroxidase
    Piperidines
    Pyrazoles
    Receptors, Cannabinoid
    Tetrazolium Salts
    Time Factors

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    17437545