McIntosh T K, Thomas M, Smith D, Banbury M
Department of Surgery, University of Connecticut Health Center, Farmington.
J Neurotrauma. 1992 Spring;9(1):33-46. doi: 10.1089/neu.1992.9.33.
The present study evaluated the effect of the nonglucocorticoid 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on the development of regional cerebral edema after lateral fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (n = 40) were anesthetized and subjected to FP brain injury of moderate severity centered over the left parietal cortex (2.5-2.6 atms). Fifteen minutes after brain injury, animals randomly received an i.v. bolus of either U74006F (3 mg/kg, n = 21) followed by a second bolus (3 mg/kg) at 3 hr or buffered sodium citrate vehicle (equal volume, n = 15). An additional group of 12 surgically prepared but uninjured animals served as preinjury controls. At 48 hr after injury, animals were sacrificed and brain tissue assayed for water content and regional cation concentrations. With the use of specific gravimetric techniques, no significant differences were observed in posttraumatic cerebral edema between drug- and control-treated animals. However, using wet weight/dry weight methodology, we found that administration of U74006F significantly reduced water content in the right hippocampus (contralateral to the site of injury) compared to saline-treated animals (p less than 0.05). U74006F also significantly prevented the postinjury increase in sodium concentrations in the ipsilateral hippocampus (p less than 0.05) and thalamus (p less than 0.03). Regional concentrations of potassium were unaltered after drug treatment. Administration of U74006F significantly reduced postinjury mortality, from 28% in control animals to zero in treated animals (p = 0.01). These results suggest that lipid peroxidation may be involved in the pathophysiological sequelae of brain injury and that 21-aminosteroids may be beneficial in the treatment of brain injury.
本研究评估了非糖皮质激素21-氨基类固醇U74006F（一种铁依赖性脂质过氧化抑制剂）对侧方液压冲击（FP）脑损伤后局部脑水肿发展的影响。雄性Sprague-Dawley大鼠（n = 40）麻醉后接受以左侧顶叶皮质为中心的中度严重程度的FP脑损伤（2.5 - 2.6个大气压）。脑损伤后15分钟，动物随机静脉推注U74006F（3 mg/kg，n = 21），3小时后再推注一次（3 mg/kg），或注射柠檬酸钠缓冲液载体（等体积，n = 15）。另外12只手术制备但未受伤的动物作为损伤前对照。损伤后48小时，处死动物并检测脑组织的含水量和局部阳离子浓度。使用特定的重量分析技术，在药物治疗组和对照组动物的创伤后脑水肿方面未观察到显著差异。然而，使用湿重/干重方法，我们发现与生理盐水治疗组动物相比，给予U74006F可显著降低右侧海马体（损伤对侧）的含水量（p < 0.05）。U74006F还显著阻止了同侧海马体（p < 0.05）和丘脑（p < 0.03）损伤后钠浓度的升高。药物治疗后局部钾浓度未改变。给予U74006F显著降低了损伤后的死亡率，从对照组动物的28%降至治疗组动物的零死亡率（p = 0.01）。这些结果表明脂质过氧化可能参与脑损伤的病理生理后遗症，并且21-氨基类固醇可能对脑损伤治疗有益。
