Oxygen free radical generation may have important secondary damaging effects after the onset of
cerebral ischemia.
Free radical scavengers have been used successfully in attenuating neuronal damage in the reperfusion period in transient forebrain
ischemia. There are limited data on effectiveness in models of focal
ischemia. Two
free radical scavengers,
alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), have been shown to reduce oxidative-stress-induced neuronal injury. Whereas PBN has been demonstrated to reduce
infarct volume in focal
ischemia, neuroprotection has not been evaluated with S-PBN. The present study was designed to evaluate the
neuroprotective effect of PBN and S-PBN compared to vehicle in a focal embolic middle cerebral artery (MCA)
cerebral ischemia model in rats. Wistar rats were randomly divided into three groups (n = 10 each group). Animals in the control group received vehicle and those in the treatment groups were treated with PBN or S-PBN (both 100 mg/kg/day x 3 days, intraperitoneally) starting 2 h after the introduction of an autologous
thrombus into the right-side MCA. The neurological outcome was observed and compared before and
after treatment and between groups. The percentage of
cerebral infarct volume was estimated from 2,3, 5-triphenyltetrazolium
chloride stained coronal slices 72 h after the ischemic insult. Two-hour postischemia administration of PBN or S-PBN significantly improved neurobehavioral scores at 24 h following MCA embolization (both P < 0.01). The percentage of
infarct volume for animals receiving vehicle was 32.8 +/- 9.4%. Two-hour delayed administration of PBN and S-PBN achieved a 35.4% reduction in
infarct volume in treatment groups when compared with animals receiving vehicle (PBN vs control, 21.2 +/- 10.9% vs 32.8 +/- 9.4%; P < 0.05; S-PBN vs control, 21.2 +/- 13.1%, (P < 0.05). These data indicate that
free radical generation may be involved in brain damage in this model and 2-h delayed postischemia treatment with PBN and S-PBN may have
neuroprotective effects in focal
cerebral ischemia. As S-PBN does not normally cross the blood-brain barrier, the neuroprotection evident in this study may be explained by entry into the brain via damaged vessels.