Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada.
Department of Surgery, Alfred Hospital, Melbourne, Australia.
Crit Care Med. 2018 Apr;46(4):554-561. doi: 10.1097/CCM.0000000000002938.
To determine profiles of serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain, examine whether erythropoietin administration reduce their concentrations, and whether biomarkers discriminate between erythropoietin and placebo treatment groups.
Single-center, prospective observational study.
A sub-study of the erythropoietin-traumatic brain injury clinical trial, conducted at the Alfred Hospital, Melbourne, Australia.
Forty-four patients with moderate-to-severe traumatic brain injury.
Epoetin alfa 40,000 IU or 1 mL sodium chloride 0.9 as subcutaneous injection within 24 hours of traumatic brain injury.
Ubiquitin carboxy-terminal hydrolase L1, phosphorylated neurofilament heavy-chain, and erythropoietin concentrations were measured in serum by enzyme-linked immunosorbent assay from D0 (within 24 hr of injury, prior to erythropoietin/vehicle administration) to D5. Biomarker concentrations were compared between injury severities, diffuse versus focal traumatic brain injury and erythropoietin or placebo treatment groups. Ubiquitin carboxy-terminal hydrolase L1 peaked at 146.0 ng/mL on D0, significantly decreased to 84.30 ng/mL on D1, and declined thereafter. Phosphorylated neurofilament heavy-chain levels were lowest at D0 and peaked on D5 at 157.9 ng/mL. D0 ubiquitin carboxy-terminal hydrolase L1 concentrations were higher in diffuse traumatic brain injury. Peak phosphorylated neurofilament heavy-chain levels on D3 and D4 correlated with Glasgow Outcome Score-Extended, predicting poor outcome. Erythropoietin did not reduce concentrations of ubiquitin carboxy-terminal hydrolase L1 or phosphorylated neurofilament heavy-chain.
Serum ubiquitin carboxy-terminal hydrolase L1 and phosphorylated neurofilament heavy-chain increase after traumatic brain injury reflecting early neuronal and progressive axonal injury. Consistent with lack of improved outcome in traumatic brain injury patients treated with erythropoietin, biomarker concentrations and profiles were not affected by erythropoietin. Pharmacokinetics of erythropoietin suggest that the dose given was possibly too low to exert neuroprotection.
确定血清泛素羧基末端水解酶 L1 和磷酸化神经丝重链的特征，检验促红细胞生成素是否能降低其浓度，以及生物标志物是否能区分促红细胞生成素和安慰剂治疗组。
单中心前瞻性观察研究。
在澳大利亚墨尔本阿尔弗雷德医院进行的促红细胞生成素创伤性脑损伤临床试验的子研究。
44 例中重度创伤性脑损伤患者。
促红细胞生成素 alfa 40000IU 或 1mL 氯化钠 0.9 作为皮下注射，在创伤性脑损伤后 24 小时内给予。
通过酶联免疫吸附试验，在血清中测量泛素羧基末端水解酶 L1、磷酸化神经丝重链和促红细胞生成素的浓度，从 D0（伤后 24 小时内，在给予促红细胞生成素/载体之前）到 D5。比较生物标志物浓度与损伤严重程度、弥漫性与局灶性创伤性脑损伤以及促红细胞生成素或安慰剂治疗组之间的差异。D0 时泛素羧基末端水解酶 L1 峰值为 146.0ng/mL，D1 时显著下降至 84.30ng/mL，此后持续下降。磷酸化神经丝重链水平在 D0 时最低，D5 时达到 157.9ng/mL 的峰值。弥漫性创伤性脑损伤时 D0 时泛素羧基末端水解酶 L1 浓度较高。D3 和 D4 时的峰值磷酸化神经丝重链水平与格拉斯哥结局评分-扩展相关，预测预后不良。促红细胞生成素并未降低泛素羧基末端水解酶 L1 或磷酸化神经丝重链的浓度。
血清泛素羧基末端水解酶 L1 和磷酸化神经丝重链在创伤性脑损伤后增加，反映了早期神经元和进行性轴突损伤。与接受促红细胞生成素治疗的创伤性脑损伤患者的结局无改善一致，生物标志物浓度和特征不受促红细胞生成素的影响。促红细胞生成素的药代动力学表明，给予的剂量可能太低，无法发挥神经保护作用。
