The protective effect of dexanabinol (HU-211) on nitric oxide and cysteine protease-mediated neuronal death in focal cerebral ischemia.
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.
Durmaz
Ramazan
R
Department of Neurosurgery, Eskişehir Osmangazi University School of Medicine, 26480, Eskisehir, Turkey. rdurmaz@ogu.edu.tr
Ozden
Hilmi
H
Kanbak
Güngör
G
Aral
Erinç
E
Arslan
Okan Can
OC
Kartkaya
Kazim
K
Uzuner
Kubilay
K
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
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