title: 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.
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Kazuhide
authors: K
authors: Hayakawa
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Kenichi
authors: K
authors: Mishima
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Masanori
authors: M
authors: Nozako
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Mai
authors: M
authors: Hazekawa
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Keiichi
authors: K
authors: Irie
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Masayuki
authors: M
authors: Fujioka
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Kensuke
authors: K
authors: Orito
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Kohji
authors: K
authors: Abe
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Nobuyoshi
authors: N
authors: Hasebe
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Nobuaki
authors: N
authors: Egashira
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Katsunori
authors: K
authors: Iwasaki
authors: Department of Neuropharmacology, Faculty of Pharmaceutical SciencesAdvanced Materials Institute, Fukuoka University, Fukuoka, JapanDepartment of Drug Safety Evaluation, Developmental Research Laboratories, Toyonaka, Osaka, JapanDepartment of Veterinary Pharmacology, School of Veterinary Medicine, Fuchinobe Sagamihara Kanagawa, Japan.
authors: Michihiro
authors: M
authors: Fujiwara
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002185:Cannabidiol / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000627:therapeutic use; D007839:Functional Laterality; D018698:Glutamic Acid / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010477:Perfusion / Q000379:methods; D009195:Peroxidase / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid / Q000502:physiology*; D000077285:Rimonabant; D013778:Tetrazolium Salts; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D013778:Tetrazolium Salts; D002185:Cannabidiol; D018698:Glutamic Acid; D013759:Dronabinol; C009591:triphenyltetrazolium; D009195:Peroxidase; D000077285:Rimonabant