Ekici M A, Uysal O, Cikriklar H I, Özbek Z, Turgut Cosan D, Baydemir C, Kazanci B, Hafizoğlu D
Neurosurgery Clinic, Ministry of Health, Sevket Yilmaz Research and Training Hospital, Bursa, Turkey.
Eur Rev Med Pharmacol Sci. 2014;18(1):10-27.
Studies in animals have provided key evidence that antagonizing TNF-α is a viable therapeutic strategy for diffuse severe brain injury. This study is planned to prevent post-traumatic secondary tissue damages in rat diffuse severe brain injury model, which is induced by alone or combined administration of Etanercept and lithium chloride (LiCl).
Male Sprague-Dawley rats were used in the current study. Rats were divided into 5 groups. Trauma was not induced and treatment was not applied to rats of Sham group. For rats of Trauma+Saline group, saline 0.9% was administered via intraperitoneal (i.p.) route at dose of 1 mg/100 g body weight 1 hour after trauma. For rats of Trauma+Etanercept group, Etanercept was administered via i.p. route at dose of 5 mg/kg body weight 1 hour after trauma. For rats of Trauma+LiCl group, LiCl was administered via i.p. route at dose of 50 mg/kg body weight 1 hour after trauma. For rats of Etanercept+LiCl group, Etanercept and LiCl were administered via i.p. route at dose of 5 mg/kg body weight and 50 mg/kg body weight, respectively, 1 hour after trauma. Serum glial fibrillary acidic protein (GFAP) and Tau levels were analyzed with ELISA. For analyses H&E, TUNEL, GFAP and TNF-α staining methods were used.
We demonstrate that Etanercept treatment reduced the TBI-induced brain tissues alteration, reduced the expression of TNF-α and improve edema and axonal swelling. We observed a significant decrease in TNF-α and GFAP positivity after LiCl was administered.
The findings obtained in this study suggest that the combination therapy with Etanercept and LiCl decreased neuronal degeneration and alleviated secondary tissue damage in post-traumatic period.
动物研究提供了关键证据，表明拮抗肿瘤坏死因子-α（TNF-α）是治疗弥漫性重度脑损伤的可行策略。本研究旨在预防大鼠弥漫性重度脑损伤模型中的创伤后继发性组织损伤，该模型通过单独或联合使用依那西普和氯化锂（LiCl）诱导。
本研究使用雄性Sprague-Dawley大鼠。大鼠分为5组。假手术组大鼠不诱导创伤且不进行治疗。创伤+生理盐水组大鼠在创伤后1小时经腹腔（i.p.）途径以1 mg/100 g体重的剂量给予0.9%生理盐水。创伤+依那西普组大鼠在创伤后1小时经腹腔途径以5 mg/kg体重的剂量给予依那西普。创伤+LiCl组大鼠在创伤后1小时经腹腔途径以50 mg/kg体重的剂量给予LiCl。依那西普+LiCl组大鼠在创伤后1小时经腹腔途径分别以5 mg/kg体重和50 mg/kg体重的剂量给予依那西普和LiCl。用酶联免疫吸附测定法（ELISA）分析血清胶质纤维酸性蛋白（GFAP）和 Tau 水平。采用苏木精-伊红（H&E）染色、末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）、GFAP 和 TNF-α 染色方法进行分析。
我们证明依那西普治疗可减轻创伤性脑损伤（TBI）引起的脑组织改变，降低 TNF-α 的表达，并改善水肿和轴突肿胀。我们观察到给予 LiCl 后 TNF-α 和 GFAP 阳性显著降低。
本研究结果表明，依那西普和 LiCl 联合治疗可减少神经元变性，并减轻创伤后时期的继发性组织损伤。
