Neurochemical Research

, 34:1157

Delayed Treatment with Carboxy-PTIO Permits a 4-h Therapeutic Window of Opportunity and Prevents Against Ischemia-Induced Energy Depletion Following Permanent Focal Cerebral Ischemia in Mice

Authors

  • E-Jian Lee
    • Neurosurgical Service, Department of SurgeryNational Cheng Kung University Hospital and Medical School
  • Yu-Chang Hung
    • Neurosurgical Service, Department of SurgeryNational Cheng Kung University Hospital and Medical School
  • Hung-Yi Chen
    • Institute of PharmacyChina Medical University
  • Tian-Shung Wu
    • Department of ChemistryNational Cheng Kung University
    • Department of Anaesthesiology, Buddhist Tzu Chi University, Tzu Chi General Hospital, Graduate Institute of Clinical MedicineTzu Chi University
Original Paper

DOI: 10.1007/s11064-008-9892-5

Cite this article as:
Lee, E., Hung, Y., Chen, H. et al. Neurochem Res (2009) 34: 1157. doi:10.1007/s11064-008-9892-5

Abstract

We examined whether a nitric oxide scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-l-oxyl-3-oxide (carboxy-PTIO), could offer neuroprotective actions and improve cerebral energy metabolism in a model of stroke. Sixty C57BL/10J mice were given either carboxy-PTIO (0.3–1.2 mg/kg) or vehicle intraperitoneally, 0.5 h after permanent middle cerebral artery occlusion, to evaluate the dose–response effects. An additional 70 animals received carboxy-PTIO (0.6 mg/kg) or vehicle, 2–6 h post-ischemia, for establishing the therapeutic window. Subgroups of animals, treated with carboxy-PTIO (0.6 mg/kg) or vehicle, were used for measuring cerebral bioenergetic metabolites (ATP, ADP, AMP, adenosine). Mice treated with carboxy-PTIO (0.6 mg/kg) had dose-specifically reduced brain infarction, significantly by 27–30% (P < 0.05), even when therapy was delayed up to 4 h after the ischemic insult (P < 0.05). Four hour post-ischemia, ATP depleted in the ischemic hemisphere (P < 0.05). Administration with carboxy-PTIO not only improved the recovery of ATP in the ischemic hemisphere (P < 0.05), but also enhanced adenosine content across the ischemic and non-ischemic hemispheres (P < 0.05). The neuroprotection of carboxy-PTIO may be partly attributed to the beneficial effects of improving cerebral energy metabolism.

Keywords

Focal cerebral ischemiaNeuroprotectionEnergy depletionCarboxy-PTIO

Copyright information

© Springer Science+Business Media, LLC 2008