HU-211, a nonpsychotropic cannabinoid, improves neurological signs and reduces brain damage after severe forebrain ischemia in rats.
The purpose of the present study was to examine the dose-response relationship and the therapeutic time window for the synthetic nonpsychotropic cannabinoid (HU-211) as a neuroprotective agent in transient, severe forebrain ischemia in the rat. Adult Sprague-Dawley rats were subjected to 20 min common carotid artery occlusion (CCAo) 24 h after coagulation of both vertebral arteries. Thirty minutes after the onset of CCAo, rats received an iv injection of HU-211 2, 4, or 8 mg/kg in HPCD (n = 12, 18, and 11, respectively), or the appropriate vehicle (n = 20). Neurological signs were scored daily for 3 d following ischemia. A significant improvement (p < 0.01, Kruskal-Wallis nonparametric test, followed by Mann-Whitney U-test, p < 0.05) of neurological deficits by the 4 mg/kg dose of HU-211, was observed 24, 48, and 72 h after insult. On the third day post-CCAo, the rat brain was taken for histopathological evaluation of the CA-1 sector of the hippocampus. Counts of viable neurons in the hippocampal CA1 field showed significantly more live cells in the HU-211 (4 mg/kg) treated animals (P < 0.001, ANOVA followed by Duncan's post-hoc test, p < 0.05). The drug was equally effective when given 30 and 60 min after ischemia, but neuroprotection was no longer significant after 3 h. We suggest that HU-211 may be a potential treatment for postischemic brain damage in human beings.
Belayev
L
L
Department of Pharmacology, Pharmos Corp., Kiryat Weizmann, Rehovot, Israel.
Bar-Joseph
A
A
Adamchik
J
J
Biegon
A
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D008297:Male; D009887:Ophthalmoscopy; D004856:Postural Balance / Q000187:drug effects; D016548:Prosencephalon / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D013997:Time Factors
D001786:Blood Glucose; D018691:Excitatory Amino Acid Antagonists; D013759:Dronabinol; C062018:HU 211