Weiss Eric, Dhir Teena, Collett Abigail, Reola Michal, Kaplan Mark, Minimo Corrado, Omert Laurel, Leung Pak
Department of Surgery, Einstein Healthcare Network, Philadelphia, PA, USA.
Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA.
Clin Exp Emerg Med. 2020 Jun;7(2):87-94. doi: 10.15441/ceem.19.050. Epub 2020 Jun 30.
Traumatic brain injury (TBI) is characterized by damage to the blood-brain barrier, inflammation, and edema formation. In this pilot study, we aimed to investigate the effects of a complement inhibitor, C1-esterase inhibitor (C1 INH), on brain edema and inflammation in a rat model of mild TBI.
Thirty-six male Sprague Dawley rats were randomly assigned to control, TBI, or TBI plus C1 INH groups. TBI and TBI plus C1 INH rats received an injection of saline or 25 IU/kg C1 INH, respectively, with TBI using a weight drop model. Control rats received saline only. Rats were subsequently euthanized and their brain tissue harvested for analysis. The primary outcome was the extent of edema as assessed by the brain's water content. Secondary outcomes included enzyme-linked immunosorbent assays to determine levels of pro-inflammatory mediators.
Tumor necrosis factor-α levels were significantly greater in TBI rats than control rats, indicating that inflammation was generated by the weight drop impact. Brain water content following TBI was significantly different between TBI rats treated with C1-INH (78.7%±0.12), untreated TBI rats (79.3%±0.12), and control rats (78.6%±0.15, P=0.001). There was a significant decrease in C3a and interleukin 2 levels among C1 INH-treated rats compared with untreated TBI rats, but no change in levels of tumor necrosis factor-α and S100β.
C1-INH inhibited the complement pathway, suggesting that C1-INH may have a therapeutic benefit in TBI. Further studies are needed to investigate the effect of C1-INH on clinical outcomes.
创伤性脑损伤（TBI）的特征是血脑屏障受损、炎症和水肿形成。在这项初步研究中，我们旨在研究补体抑制剂C1酯酶抑制剂（C1 INH）对轻度TBI大鼠模型脑水肿和炎症的影响。
36只雄性Sprague Dawley大鼠被随机分为对照组、TBI组或TBI加C1 INH组。TBI组和TBI加C1 INH组大鼠分别接受生理盐水或25 IU/kg C1 INH注射，TBI采用重物坠落模型。对照组大鼠仅接受生理盐水。随后对大鼠实施安乐死并采集脑组织进行分析。主要结局是通过脑含水量评估的水肿程度。次要结局包括酶联免疫吸附测定以确定促炎介质水平。
TBI大鼠的肿瘤坏死因子-α水平显著高于对照组大鼠，表明重物坠落撞击引发了炎症。TBI后，接受C1-INH治疗的TBI大鼠（78.7%±0.12）、未治疗的TBI大鼠（79.3%±0.12）和对照组大鼠（78.6%±0.15，P=0.001）的脑含水量存在显著差异。与未治疗的TBI大鼠相比，C1 INH治疗的大鼠中C3a和白细胞介素2水平显著降低，但肿瘤坏死因子-α和S100β水平没有变化。
C1-INH抑制了补体途径，表明C1-INH可能对TBI具有治疗益处。需要进一步研究来调查C1-INH对临床结局的影响。
