Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury

There is evidence that the excessive generation of reactive-oxygen radicals contributes to the brain injury associated with transient, cerebral ischem ia. This study investigates the effects of tempol, a small, water-soluble m olecule, that crosses biological membranes, on the brain injury caused by b ilateral occlusion and reperfusion of both common carotid arteries in the g erbil (BCO), Treatment of gerbils with tempol (30 mg/kg i.p. at 30 min prio r to reperfusion and at 1 and 6 h after the onset of reperfusion) reduced t he formation of post-ischemic brain oedema. Tempol also attenuated the incr ease in the cerebral levels of malondialdehyde (MDA) and the hippocampal le vels of myeloperoxidase (MPO) caused by cerebral ischemia and reperfusion. The immunohistochemical analysis of the hippocampal region of brains subjec ted to ischemia-reperfusion exhibited positive staining for nitrotyrosine ( an indicator of the generation of peroxynitrite) and poly(ADP-ribose) synth etase (PARS) (an indicator of the activation of this nuclear enzyme seconda ry to single strand breaks in DNA). in gerbils subjected to BCO, which were treated with tempol, the degree of staining fur nitrotyrosine and PARS was markedly reduced. Tempol increased survival and reduced the hyperactivity (secondary to the ischemia-induced neurodegeneration) caused by cerebral is chemia and reperfusion. The loss of neurons from the pyramidal layer of the CAI region caused by ischemia and reperfusion was also attenuated by treat ment of gerbils with tempol, This is the first evidence that the membrane-p ermeable, radical scavenger tempol reduces the cerebral injury caused by tr ansient, cerebral ischemia in vivo. (C) 2000 Elsevier Science B.V. All righ ts reserved.