EFFECTS OF DIMETHYLTHIOUREA ON SELECTIVE NEURONAL VULNERABILITY IN FOREBRAIN ISCHEMIA IN RATS

Background and Purpose: Attempts have been made to characterize condit ions under which oxygen free radicals contribute to ischemic brain dam age. According to one hypothesis, free radicals are likely mediators o f damage only when ischemia is of such long duration that infarction d evelops or when either preischemic hyperglycemia or hyperthermia is pr esent. The objective of the present study was to explore whether 15 mi nutes of forebrain ischemia, an insult that leads to selective neurona l vulnerability but not to infarction, is accompanied by production of pathogenetically important free radicals. Methods: Using a histopatho logical end point, we studied amelioration of damage by a free radical scavenger, dimethylthiourea, administered in a dose of 750 mg/kg i.p. 60 minutes before ischemia. To study whether this insult leads to det ectable protein oxidation we assessed the activity of glutamine synthe tase and of carbonyl compounds in the soluble protein fraction. Result s: In control animals, the transient ischemia resulted in the expected damage to vulnerable neurons in hippocampus, caudoputamen, and neocor tex after 7 days of recovery. Glutamine synthetase activity in caudopu tamen and hippocampus and carbonyl content in the soluble protein frac tion after 90 minutes of recovery were not affected. However, dimethyl thiourea significantly reduced damage to hippocampus and caudoputamen (p<0.001) and neocortex (p<0.005). Conclusions. Lack of evidence of pr otein oxidation supports the notion that 15 minutes of forebrain ische mia results in a limited insult, confined to the neurons. Provided tha t unspecific effects can be excluded, the results obtained with dimeth ylthiourea suggest that free radicals contribute to selective neuronal necrosis.