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

  • E-Jian Lee
  • Yu-Chang Hung
  • Hung-Yi Chen
  • Tian-Shung Wu
  • Tsung-Ying Chen
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

Authors and Affiliations

  • E-Jian Lee
    • 1
  • Yu-Chang Hung
    • 1
  • Hung-Yi Chen
    • 2
  • Tian-Shung Wu
    • 3
  • Tsung-Ying Chen
    • 4
  1. 1.Neurosurgical Service, Department of SurgeryNational Cheng Kung University Hospital and Medical SchoolTainanTaiwan
  2. 2.Institute of PharmacyChina Medical UniversityTaichungTaiwan
  3. 3.Department of ChemistryNational Cheng Kung UniversityTainanTaiwan
  4. 4.Department of Anaesthesiology, Buddhist Tzu Chi University, Tzu Chi General Hospital, Graduate Institute of Clinical MedicineTzu Chi UniversityHualienTaiwan