title: The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.
abstract: We hypothesized that dexanabinol can prevent neuronal death by protecting neuronal lysosomes from nitric oxide (NO)-mediated toxicity, and in turn, by suppressing the release of cathepsins during cerebral ischemia. Focal cerebral ischemia was induced in two sets of animals by permanent middle cerebral artery occlusion. The first set was used to monitor NO concentration and cathepsin activity, while the second was used for histological examination with hematoxylin and eosin, and TUNEL staining. In post-ischemic brain tissue, NO content and cathepsin B and L activity increased (p < 0.05). Dexanabinol treatment reduced NO concentration and cathepsin activity to the control level (p > 0.05). The number of eosinophilic and apoptotic neurons increased in the post-ischemic cerebral cortex (p < 0.05). However, dexanabinol treatment lowered both of these (p < 0.05). We conclude that dexanabinol might be a useful agent for the treatment of stroke patients.
authors.affiliation: Department of Neurosurgery, Eskişehir Osmangazi University School of Medicine, 26480, Eskisehir, Turkey. rdurmaz@ogu.edu.tr
authors.forename: Ramazan
authors.initials: R
authors.lastname: Durmaz
authors.forename: Hilmi
authors.initials: H
authors.lastname: Ozden
authors.forename: Güngör
authors.initials: G
authors.lastname: Kanbak
authors.forename: Erinç
authors.initials: E
authors.lastname: Aral
authors.forename: Okan Can
authors.initials: OC
authors.lastname: Arslan
authors.forename: Kazim
authors.initials: K
authors.lastname: Kartkaya
authors.forename: Kubilay
authors.initials: K
authors.lastname: Uzuner
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D013759:Dronabinol; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534280:Ctsl protein, rat; C062018:HU 211