Dimethylthiourea Reduces Ischemic Brain Edema without Affecting Cerebral Blood Flow

Abstract

Oxygen free radicals have been implicated as mediators of tissue damage in ischemic brain. We previously demonstrated that the hydroxyl radical scavenger 1,3-dimethyl-2-thiourea (DMTU) reduces infarct size after middle cerebral artery occlusion (MCAO) in rats. The present study was undertaken to determine whether this protection results from a preservation of the CBF. Adult male Sprague-Dawley rats were treated with DMTU (750 mg/kg i.p.) or saline vehicle 1 h before right MCAO. One-half, 4, or 24 h after MCAO, animals were killed and samples were taken from the central, intermediate, and outer zones of the MCA distribution of each cortical mantle. Separate groups of animals were used to analyze these samples for water content (wet and dry weight), CBF ([14C]butanol), or blood–brain barrier permeability ([3H]α-aminoisobutyric acid). CBF was reduced in a graded fashion in the ischemic cortex: 0.169 ± 0.020, 0.261 ± 0.017, and 0.435 ± 0.023 ml/g/min (mean ± SEM, n = 8) after 4 h in the central, intermediate, and outer zones, respectively. Brain edema was present in a similar pattern, while blood–brain barrier permeability remained normal. Treatment with DMTU significantly reduced brain edema in the central and intermediate zones at both 4 and 24 h. However, CBF in the DMTU-treated animals was identical to that of the vehicle-treated animals. These results suggest that hydroxyl radicals play a role in the development of ischemic brain edema, but the mechanism does not appear to involve a direct effect on CBF.