Uridine 5′-triphosphate (UTP) protects against cerebral ischemia reperfusion injury in rats

• Published in: Neuroscience letters 2009-11, Vol.465 (1), p.55-60
• Main Authors: Tian, Mou-Li, Zou, Zui, Yuan, Hong-Bing, Wang, Cheng-Cai, Zhu, Qiu-Feng, Xu, Hai-Tao, Gao, Xin, Shi, Xue-Yin
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain - pathology; Cell Death - drug effects; Cerebral ischemia reperfusion; Cerebrovascular Disorders - drug therapy; Cerebrovascular Disorders - metabolism; Cerebrovascular Disorders - pathology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Magnetic Resonance Imaging; Male; Medical sciences; Microscopy, Electron; Neurology; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Severity of Illness Index; Tetrazolium Salts; Uridine Triphosphate - administration & dosage; Uridine Triphosphate - pharmacology; UTP; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; Water - metabolism
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.08.076

Aims: To test the hypothesis that uridine 5′-triphosphate (UTP) had a protective effect on cerebral ischemia reperfusion (IR) injury in rats. Methods: Ischemia was induced by intraluminal suture of middle cerebral artery occlusion (MCAO). UTP solution was delivered through an indwelling tail venous catheter via microinfusion pump 30 min after the occlusion of MCA at a rate of 0.5 ml/100 g/min. Neurological deficit score (NDS) and brain water content were determined 24 h after reperfusion. Infarct volume was determined by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and magnetic resonance imaging (MRI), and nerve cell death was studied under an electron microscope. Results: There was a dose-dependent relationship among 10, 30 and 90 μg/kg UTP. The 90 μg/kg UTP had the best protective effect among the 3 groups. We compared 90 μg/kg UTP group with normal saline group and found that UTP had a protective effect on cerebral IR by the results of TTC staining (15.9% vs 30.5%, P < 0.01). MRI at 6, 30 and 54 h after reperfusion showed smaller infarct volume in 90 μg/kg group compared with 0 μg/kg group (283.5, 352.1, 367.45 mm 3 vs 401.36, 576.75 and 677.11 mm 3, respectively), and electron microscope showed less nerve cell death in 90 μg/kg group compared with 0 μg/kg group. Conclusion: UTP has a dose-dependent protective effect on cerebral IR.