Involvement of free radicals in cerebral vascular reperfusion injury evaluated in a transient focal cerebral ischemia model of rat

Free Radic Biol Med. 1999 Mar;26(5-6):722-9. doi: 10.1016/s0891-5849(98)00257-3.


Free radicals have been suggested to be largely involved in the genesis of ischemic brain damage, as shown in the protective effects of alpha-phenyl-N-tert-butyl nitrone (PBN), a spin trapping agent, against ischemic cerebral injury. In the present study, the effects of PBN as well as MCI-186, a newly-developed free radical scavenger, and oxypurinol, an inhibitor of xanthine oxidase, were evaluated in a rat transient middle cerebral aretery (MCA) occlusion model to clarify the possible role of free radicals in the reperfusion injury of brain. The volume of cerebral infarction, induced by 2-h occlusion and subsequent 2-h reperfusion of MCA in Fisher-344 rats, was evaluated. The administration of PBN (100 mg/kg) and MCI-186 (100 mg/kg) just before reperfusion of MCA significantly reduced the infarction volume. In contrast, oxypurinol (100 mg/kg) failed to show any preventive effect on the infarction. These results suggest that free radical formation is involved in the cerebral damage induced by ischemia-reperfusion of MCA, and that hydroxyl radical is responsible for the reperfusion injury after transient focal brain ischemia. It is also suggested that xanthine oxidase is not a major source of free radicals.

MeSH terms

  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Brain / drug effects*
  • Brain / pathology
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / pathology
  • Cerebral Infarction / pathology
  • Cerebral Infarction / physiopathology
  • Cerebral Infarction / prevention & control*
  • Cyclic N-Oxides
  • Disease Models, Animal
  • Edaravone
  • Free Radical Scavengers / pharmacology*
  • Free Radicals / metabolism
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Ischemic Attack, Transient / pathology
  • Ischemic Attack, Transient / physiopathology*
  • Male
  • Nitroarginine / pharmacology
  • Nitrogen Oxides / pharmacology*
  • Putamen / drug effects
  • Putamen / pathology
  • Rats
  • Rats, Inbred F344
  • Rats, Wistar
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology*
  • Reperfusion Injury / prevention & control*
  • Spin Labels
  • Superior Colliculi / drug effects
  • Superior Colliculi / pathology


  • Cyclic N-Oxides
  • Free Radical Scavengers
  • Free Radicals
  • Nitrogen Oxides
  • Spin Labels
  • Nitroarginine
  • phenyl-N-tert-butylnitrone
  • Edaravone
  • Antipyrine