Dexanabinol; a novel neuroprotective drug in experimental focal cerebral ischemia.
The permanent middle cerebral artery occlusion (PMCAO) model was used to investigate the cerebroprotective effects of the synthetic cannabinoid, dexanabinol (HU-211). Dexanabinol is a noncompetitive N-methyl-D-aspartate antagonist, with antioxidant and anti-TNFalpha properties. Twenty hypertensive rats were subjected to PMCAO. Eight were given 4 mg/kg dexanabinol, i.v., 1 h after PMCAO, eight received vehicle and four were not injected Five rats underwent sham surgery. Infarct volumes were assessed, as well as TNFalpha concentrations and NOS activity in brain homogenates. Dexanabinol significantly decreased infarct volumes. It also significantly lowered TNFalpha levels in the ipsilateral hemisphere although not to the level of sham operated rats. No effect could be demonstrated on NOS activity. In conclusion, dexanabinol may be a pluripotent cerebroprotective agent.
Leker
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RR
Department of Neurology, Hebrew University-Hadassah Medical School, Jerusalem, Israel. leker@cc.huji.ac.il
Shohami
E
E
Abramsky
O
O
Ovadia
H
H
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006973:Hypertension / Q000150:complications*; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D013759:Dronabinol; D019001:Nitric Oxide Synthase; C062018:HU 211