Neuroprotection by the alpha2-adrenoceptor agonist, dexmedetomidine, in rat focal cerebral ischemia.
The present study was undertaken to explore the possible neuroprotective effect of the selective alpha2-adrenoceptor agonist, dexmedetomidine in a rat model of focal cerebral ischemia. The effect of dexmedetomidine (9 microg kg(-1)) on infarct volume was assessed and compared to that of glutamate receptor antagonists cis-4(phosphonomethyl)-2-piperidine carboxylic acid (CGS-19755) (20 mg kg(-1)) or 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) (50 mg kg(-1)). Dexmedetomidine decreased total ischemic volume by 40% in the cortex (P<0.05) compared to NaCl-treated control rats, whereas NBQX reduced the infarct by 73% in the cortex (P<0.001) and by 43% in the striatum (P<0.01). Dexmedetomidine infusion was associated with some minor degree of hyperglycemia and hypotension. Drug-induced kidney changes were only seen in NBQX-treated rats. These results suggest that dexmedetomidine reduced ischemic volume despite causing a minor increase in blood glucose concentrations and hypotension. Its neuroprotective efficacy was better than that produced by CGS-19775, and dexmedetomidine was safer with respect to kidney toxicity when compared to NBQX.
Jolkkonen
J
J
Department of Neurology, University of Kuopio, Finland. jukka.jolkkonen@uku.fi
Puurunen
K
K
Koistinaho
J
J
Kauppinen
R
R
Haapalinna
A
A
Nieminen
L
L
Sivenius
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D002536:Cerebral Arteries / Q000503:physiopathology / Q000601:surgery; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D020926:Medetomidine; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D018696:Neuroprotective Agents; D010875:Pipecolic Acids; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C053672:selfotel; D020926:Medetomidine