Therapeutic evaluation of etanercept in a model of traumatic brain injury
Therapeutic evaluation of etanercept in a model of traumatic brain injury
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DOI：
10.1111/j.1471-4159.2010.06969.x
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发表时间：
2010-11-01
影响因子：
4.7
通讯作者：
Chang, Ching-Ping
中科院分区：
文献类型：
--
作者：
Chio, Chung-Ching;Lin, Jia-Wei;Chang, Ching-Ping
依那西普拮抗肿瘤坏死因子-α已被证明在治疗脊髓损伤和中枢性内毒素诱导的脑损伤中有效。然而，依那西普可能提供治疗创伤性脑损伤（TBI）的希望。在本研究中，麻醉大鼠在TBI发作后立即分为两个主要组，并连续3天每12小时腹膜内给予溶媒溶液（1 mL/kg体重）或依那西普（5 mg/kg体重）。依那西普引起TBI诱导的脑缺血（例如，谷氨酸盐和乳酸盐/丙酮酸盐比率的细胞水平增加），损伤（例如，甘油的细胞水平增加）和挫伤以及运动和认知功能缺陷。TBI诱导的神经元凋亡（例如，末端脱氧核苷酸转移酶α UTP切口末端标记和神经元特异性核蛋白双阳性细胞的数量增加），神经胶质细胞凋亡（例如，末端脱氧核苷酸转移酶α UTP缺口末端标记和胶质纤维酸性蛋白双阳性细胞数量增加）、星形胶质细胞（例如，胶质细胞酸性蛋白阳性细胞数目增加）和小胶质细胞（例如，离子化的钙结合衔接分子1阳性细胞数目的增加）活化和活化的炎症（例如，肿瘤坏死因子-α、白细胞介素-1 β和白细胞介素-6的水平升高）均被依那西普治疗显著降低。这些发现表明依那西普可能通过渗透到大鼠的脑脊液中来改善TBI的结局。
P>Antagonism of tumor necrosis factor-alpha with etanercept has proved to be effective in the treatment of spinal cord injury and centrally endotoxin-induced brain injury. However, etanercept may offer promise as therapy for traumatic brain injury (TBI). In this study, anesthetized rats, immediately after the onset of TBI, were divided into two major groups and given the vehicle solution (1 mL/kg of body weight) or etanercept (5 mg/kg of body weight) intraperitoneally once per 12 h for consecutive 3 days. Etanercept caused attenuation of TBI-induced cerebral ischemia (e.g., increased cellular levels of glutamate and lactate-to-pyruvate ratio), damage (e.g., increased cellular levels of glycerol) and contusion and motor and cognitive function deficits. TBI-induced neuronal apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase alpha UTP nick-end labeling and neuronal-specific nuclear protein double-positive cells), glial apoptosis (e.g., increased numbers of terminal deoxynucleotidyl transferase alpha UTP nick-end labeling and glial fibrillary acidic protein double-positive cells), astrocytic (e.g., increased numbers of glial fibrillary acidic protein positive cells) and microglial (e.g., increased numbers of ionized calcium-binding adapter molecule 1-positive cells) activation and activated inflammation (e.g., increased levels of tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) were all significantly reduced by etanercept treatment. These findings suggest that etanercept may improve outcomes of TBI by penetrating into the cerebrospinal fluid in rats.