Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article.
Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome: clinical article.
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DOI：
10.3171/2012.9.jns12815
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发表时间：
2012-12
影响因子：
4.1
通讯作者：
Keane RW
中科院分区：
文献类型：
--
作者：
Adamczak S;Dale G;de Rivero Vaccari JP;Bullock MR;Dietrich WD;Keane RW
创伤性脑损伤 (TBI) 是第三大常见的中枢神经系统 (CNS) 病理，困扰着 530 万患有与 TBI 相关的永久性残疾的美国人。为了评估损伤的严重程度和预后，医生依靠临床变量。在这里，我们寻求反映中枢神经系统特有的分子损伤机制的客观生化标记，作为损伤严重程度和结果的更准确测量。其中一种继发性损伤机制是先天免疫反应，它受到炎症小体的调节，炎症小体是一种激活 caspase-1 和 interleukin-1β 的分子平台。我们研究了 23 名 TBI 患者的脑脊液 (CSF) 中是否存在炎症小体成分，以及炎症小体成分的水平是否与结果相关。我们对 TBI 患者和非创伤对照的脑脊液样本进行了免疫印迹分析，并通过格拉斯哥结果量表 (GOS) 评估了受伤后五个月的结果。通过曼-惠特尼 U 检验和线性回归分析对数据进行分析。与非创伤对照相比，重度或中度颅骨创伤患者的脑脊液中炎症体蛋白凋亡相关斑点样蛋白（包含 caspase 募集结构域 (ASC)、caspase-1 和 NAcht 富含亮氨酸重复蛋白-1 (NALP-1)）的水平显着升高（P < 0.0001；P = 0.0029；P = 0.0202， 分别）。损伤后 5 个月时每种蛋白的表达与 GOS 显着相关（P < 0.05）。出现不良结局（包括死亡和严重残疾）的患者脑脊液中 ASC、caspase-1 和 NALP-1 显着升高（P < 0.0001）。 NALP-1 炎性体蛋白是评估 TBI 严重程度、结果和阻碍恢复的继发性损伤机制的潜在生物标志物，可作为临床预测因子的辅助手段。
Traumatic brain injury (TBI), the third most common central nervous system (CNS) pathology, plagues 5.3 million Americans with permanent TBI-related disabilities. To evaluate injury severity and prognosis, physicians rely on clinical variables. Here we seek objective, biochemical markers reflecting molecular injury mechanisms specific to the CNS as more accurate measurements of injury severity and outcome. One such secondary injury mechanism, the innate immune response, is regulated by the inflammasome, a molecular platform that activates caspase-1 and interleukin-1β. We investigated whether inflammasome components are present in the cerebrospinal fluid (CSF) of 23 TBI patients, and whether levels of inflammasome components correlate with outcome. We performed immunoblot analysis of CSF samples from TBI patients and non-trauma controls and assessed outcome five months post-injury by the Glasgow Outcome Scale (GOS). Data were analyzed by Mann-Whitney U tests and linear regression analysis. Patients with severe or moderate cranial trauma exhibited significantly higher CSF levels of the inflammasome proteins apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and NAcht leucine-rich-repeat protein-1 (NALP-1) compared to non-trauma controls (P < 0.0001; P = 0.0029; P = 0.0202, respectively). Expression of each protein correlated significantly with GOS at five months post-injury (P < 0.05). ASC, caspase-1, and NALP-1 were significantly higher in the CSF of patients with unfavorable outcomes, including death and severe disability (P < 0.0001). NALP-1 inflammasome proteins are potential biomarkers to assess TBI severity, outcome, and the secondary injury mechanisms impeding recovery, serving as adjuncts to clinical predictors.