Belayev Ludmila, Becker David A, Alonso Ofelia F, Liu Yitao, Busto Raul, Ley James J, Ginsberg Myron D
Department of Neurology, Cerebral Vascular Disease Research Center, University of Miami School of Medicine, Florida 33101, USA.
J Neurosurg. 2002 Jun;96(6):1077-83. doi: 10.3171/jns.2002.96.6.1077.
Stilbazulenyl nitrone (STAZN) is a second-generation azulenyl nitrone that has markedly enhanced antioxidant properties compared with those of conventional alpha-phenyl nitrones. In this study, the authors assessed the potential efficacy of STAZN in a rodent model of fluid-percussion brain injury, which results in a consistent cortical contusion.
After anesthesia had been induced in normothermic Sprague-Dawley rats (brain temperature 36-36.5 degrees C) by halothane-nitrous oxide, the animals were subjected to a right parietooccipital parasagittal fluid-percussion injury (1.5-2 atm). The agent (STAZN, 30 mg/kg: eight animals) or vehicle (dimethyl sulfoxide; eight animals) was administered intraperitoneally at 5 minutes and 4 hours after trauma. The neurological status of each rat was evaluated on Days 1, 2, and 7 postinjury (normal score 0, maximum injury 12). Seven days after trauma, the rat brains were perfusion fixed, coronal sections at various levels were digitized, and areas of contusion were measured. Treatment with STAZN significantly improved neurological scores on Days 2 and 7 postinjury compared with vehicle-treated rats. Administration of STAZN also significantly reduced the total contusion area by 63% (1.8 +/- 0.5 mm2 in STAZN-treated animals compared with 4.8 +/- 2.1 mm2 in vehicle-treated animals; p = 0.04) and the deep cortical contusion area by 60% (1.2 +/- 0.2 mm2 in STAZN-treated animals compared with 2.9 +/- 1.2 mm2 in vehicle-treated animals; p = 0.03). By contrast, hippocampal cell loss in the CA3 sector was unaffected by STAZN treatment.
Therapy with STAZN, a novel potent antioxidant, administered following traumatic brain injury, markedly improves neurological and histological outcomes. Azulenyl nitrones appear to represent a promising class of neuroprotective agents for combating this devastating condition.
芪并薁基硝酮（STAZN）是第二代薁基硝酮，与传统的α-苯基硝酮相比，其抗氧化性能显著增强。在本研究中，作者评估了STAZN在流体冲击性脑损伤啮齿动物模型中的潜在疗效，该模型会导致一致的皮质挫伤。
用氟烷-氧化亚氮对正常体温的Sprague-Dawley大鼠（脑温36-36.5摄氏度）进行麻醉后，对动物进行右顶枕矢状旁流体冲击性损伤（1.5-2个大气压）。在创伤后5分钟和4小时腹腔注射药物（STAZN，30mg/kg：8只动物）或溶剂（二甲基亚砜；8只动物）。在损伤后第1、2和7天评估每只大鼠的神经状态（正常评分0，最大损伤12）。创伤7天后，对大鼠脑进行灌注固定，将不同水平的冠状切片数字化，并测量挫伤面积。与溶剂处理的大鼠相比，STAZN处理显著改善了损伤后第2天和第7天的神经评分。给予STAZN还显著减少了总挫伤面积63%（STAZN处理的动物为1.8±0.5平方毫米，而溶剂处理的动物为4.8±2.1平方毫米；p=0.04），深部皮质挫伤面积减少了60%（STAZN处理的动物为1.2±0.2平方毫米，而溶剂处理的动物为2.9±1.2平方毫米；p=0.03）。相比之下，STAZN处理对CA3区海马细胞丢失没有影响。
新型强效抗氧化剂STAZN在创伤性脑损伤后进行治疗，可显著改善神经和组织学结果。薁基硝酮似乎是一类有前途的神经保护剂，可用于对抗这种破坏性疾病。
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