Effect of 21-aminosteroid U74389G on the Extent of Brain Damage and Edema in the Newborn Rats with Hypoxic-ischemic Injury

ABSTRACT

PURPOSE: To investigate the effect of 21-aminosteroid U74389G (U) on the extent of brain damage and edema formation in the newborn rats with hypoxic ischemic (HI) brain injury. METHODS: This is a randomized, placebo-controlled, experimental study. The subjects were 113 seven-days-old rats with HI injury. Pups were treated with 3, 10, or 20 mg/ kg of U intraperitoneally 30 minutes before hypoxia (Group 1, 2, 3 n=10, 13, 11), 10 mg/kg of U immediately after hypoxia (n=11) (Group 4), 10 mg/kg of U 30 minutes before and after hypoxia (n=n=13) (Group 5), or vehicle (n=12) (Group C). We expressed the degree of brain infarction and brain edema in % atrophy (Left hemisphere-Right hemisphere/Left hemispherex100) and water content % (wet weight-dry weight/wet weightx100) RESULTS: There were significant reductions in the diameters of right hemisphere compared with those of left hemisphere in vehicle and U treated animals (P<0.05). As to the cortical thickness, group 2, 3 and 5 pups showed no significant reductions in the right side compared with the left side implicating that U treatment in these groups was of benefit in attenuating HI cortical injury, while there was significant difference between the right and left side in group 1, 4 and C animals (P<0.001). There was a significant difference (P< 0.01) in % atrophy of group 2, 3, 5 versus group C, but the mean % atrophy was similar in groups 1, 4 and C. There was a significant (P<0.05) increase of water content in right hemisphere compared with left hemisphere both in U and vehicle treated groups. CONCLUSION: Pre-treatment and prepost-treatment at moderate doses (10 or more mg/kg) of 21-aminosteroid U74389G reduced the extent of perinatal hypoxic-ischemic brain damages, especially in the cortex, but do not affect the extent of brain edema.