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

Neurosci Lett. 2009 Nov 6;465(1):55-60. doi: 10.1016/j.neulet.2009.08.076. Epub 2009 Sep 3.

Abstract

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 microg/kg UTP. The 90 microg/kg UTP had the best protective effect among the 3 groups. We compared 90 microg/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 microg/kg group compared with 0 microg/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 microg/kg group compared with 0 microg/kg group.

Conclusion: UTP has a dose-dependent protective effect on cerebral IR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Death / drug effects
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / metabolism
  • Cerebrovascular Disorders / pathology
  • Dose-Response Relationship, Drug
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Magnetic Resonance Imaging
  • Male
  • Microscopy, Electron
  • 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*
  • Water / metabolism

Substances

  • Neuroprotective Agents
  • Tetrazolium Salts
  • Water
  • triphenyltetrazolium
  • Uridine Triphosphate