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.
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Authors | N Jiang, E A Kowaluk, C H Lee, H Mazdiyasni, M Chopp |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 320
Issue 2-3
Pg. 131-7
(Feb 12 1997)
ISSN: 0014-2999 [Print] Netherlands |
PMID | 9059845
(Publication Type: Journal Article)
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Chemical References |
- 5'-deoxy-5-iodotubercidin
- Enzyme Inhibitors
- Neuroprotective Agents
- Adenosine Kinase
- Tubercidin
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Topics |
- Adenosine Kinase
(antagonists & inhibitors)
- Animals
- Arterial Occlusive Diseases
(complications)
- Body Temperature
(drug effects)
- Body Weight
(drug effects)
- Brain
(drug effects, enzymology, physiology)
- Cerebral Infarction
(etiology, prevention & control)
- Enzyme Inhibitors
(therapeutic use)
- Ischemic Attack, Transient
(prevention & control)
- Male
- Neuroprotective Agents
(therapeutic use)
- Rats
- Rats, Wistar
- Tubercidin
(analogs & derivatives, therapeutic use)
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