title: Adenosine kinase inhibition protects brain against transient focal ischemia in rats.
abstract: Endogenous adenosine released locally during cerebral ischemia is neuroprotective, and agents which decrease adenosine inactivation may potentiate its protective effects. The effects of 5'-deoxy-5-iodotubercidin (5'd-5IT), an inhibitor of the adenosine-catabolizing enzyme, adenosine kinase, were studied in male Wistar rats subjected to 2 h of transient middle cerebral artery occlusion. 5'd-5IT or the vehicle (10% DMSO in saline) was administered i.p. 30 min before, and 2 h and 6 h after the induction of middle cerebral artery occlusion. The infarct volume was determine using 2,3,5-triphenyltetrazolium chloride staining 48 h after middle cerebral artery occlusion. The infarct volume was significantly reduced in rats treated with 1.85 mg/kg x 3 (57% reduction, P < 0.001) or 1.0 mg/kg x 3 (34% reduction, P < 0.05), but not 0.3 mg/kg x 3 5'd-5IT compared to vehicle-treated rats. The reduction of infarct volume was accompanied by a significant improvement in behavioral measures of neurological deficit. These data further support a role of adenosine in neuroprotection and suggest that adenosine kinase inhibition may be a useful approach to the treatment of focal cerebral ischemia.
authors.affiliation: Henry Ford Health Science Center, Department of Neurology, Detroit, MI 48202, USA.
authors.forename: N
authors.initials: N
authors.lastname: Jiang
authors.forename: E A
authors.initials: EA
authors.lastname: Kowaluk
authors.forename: C H
authors.initials: CH
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Mazdiyasni
authors.forename: M
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D002544:Cerebral Infarction / Q000209:etiology / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014372:Tubercidin / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: C040541:5'-deoxy-5-iodotubercidin; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D000248:Adenosine Kinase; D014372:Tubercidin