The effect of the free radical spin-trap alpha-phenyl-butyl-tert-nitrone 
(alpha-PBN) in permanent focal cerebral ischemia in rats was examined in two 
series of experiments. In the first, rats were subjected to permanent occlusion 
of the middle cerebral artery (MCAO) and treated 1 h after occlusion with a 
single dose of alpha-PBN (100 mg/kg) or saline. Body temperature was measured 
and controlled for the first 24 h to obtain identical temperature curves in the 
two groups. Cortical infarct volumes were determined on histological sections 7 
days later. alpha-PBN did not significantly reduce infarct volume (control: 
28.3+/-16.3 mm3 vs. alpha-PBN 23.7+/-7.4 mm3). In the second series of 
experiments, periinfarct depolarizations (PIDs) were recorded with an 
extracellular DC electrode at two locations in the ischemic penumbra for the 
initial 3 h following MCAO. alpha-PBN (100 mg/kg, single dose in conjunction 
with occlusion) significantly reduced the total number (median value of 3 PIDs 
in the control groups vs. 1 PID in alpha-PBN groups, p<0.001) and total duration 
of the PIDs (median value 662 s in the control groups vs. 162 s in the alpha-PBN 
groups, p<0.006). In spite of this, cortical infarct volumes determined 7 days 
later in the same rats were not smaller in alpha-PBN-treated rats. The study 
thus demonstrates that attenuation of PIDs does not always lead to smaller 
infarcts if permanent arterial occlusion is followed by long survival time and 
does not support the hypothesis that PIDs per se are critical determinants of 
infarct size in this situation.