MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat
MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat
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MMP-9 抑制剂 SB-3CT 可减轻大鼠脑外伤后的行为障碍和海马损失。
DOI：
10.1089/neu.2013.3230
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发表时间：
2014-07-01
影响因子：
4.2
通讯作者：
Jiang, Ji-yao
中科院分区：
文献类型：
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作者：
Jia, Feng;Yin, Yu Hua;Jiang, Ji-yao
本研究的目的是评估SB-3CT，一种基质金属肽酶9抑制剂，对大鼠创伤性脑损伤（TBI）后行为和组织学结果的潜在疗效。将成年雄性Sprague-Dawley大鼠随机分为三组（n=15/组）：用SB-3CT治疗的TBI、用盐水治疗的TBI和假损伤。采用液压冲击式颅脑损伤装置建立颅脑损伤模型。在TBI后30分钟、6小时和12小时腹膜内施用SB-3CT（在10%二甲基亚砜中50 mg/kg）。分别在术后第1-5天和第11- 1 - 5天评估运动功能（平衡木/行走试验）和空间学习/记忆（Morris水迷宫）。分别于伤后24 h、72 h和15 d行Fluoro-Jade染色、免疫荧光和甲酚紫染色进行组织病理学评价。研究表明，TBI可导致由急性神经变性、裂解的caspase-3表达增加和长期神经元损失诱导的显著行为缺陷。SB-3CT干预通过目前的制度提供了强大的行为保护和海马神经元保护TBI的有害影响。因此，可以确定SB-3CT对TBI预后的有效性。据信，目前的研究增加了越来越多的文献，将SB-3CT确定为人类脑损伤的潜在治疗方法。
The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix metallopeptidase 9 inhibitor, on behavioral and histological outcomes after traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n=15/group): TBI with SB-3CT treatment, TBI with saline, and sham injury. The TBI model was induced by a fluid percussion TBI device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative Days 1-5 and 11-15, respectively. Fluoro-Jade staining, immunofluorescence, and cresyl violet-staining were carried out for histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively. It was shown that TBI can result in significant behavioral deficit induced by acute neurodegeneration, increased expression of cleaved caspase-3, and long-term neuronal loss. SB-3CT intervention via the current regime provides robust behavioral protection and hippocampal neurons preservation from the deleterious effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be ascertained. It is believed that the current study adds to the growing literature in identifying SB-3CT as a potential therapy for human brain injury.