The free radical spin-trap alpha-PBN attenuates periinfarct depolarizations following permanent middle cerebral artery occlusion in rats without reducing infarct volume.
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.
Laboratory of Neuropathology, Institute of Molecular Pathology, University of Copenhagen, Frederik V's vej 11, 6th Floor, DK-2100 Copenhagen, Denmark. tc@dadlnet.dk
Thomas
T
Christensen
Torben
T
Bruhn
Nils Henrik
NH
Diemer
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D013181:Cortical Spreading Depression / Q000187:drug effects; D003497:Cyclic N-Oxides; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D005609:Free Radicals / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013534:Survival; D013997:Time Factors
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D005904:Glial Fibrillary Acidic Protein; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D011189:Potassium Chloride