The Miami Project to Cure Paralysis, Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Medical Scientist Training Program, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Cells. 2024 Aug 17;13(16):1370. doi: 10.3390/cells13161370.
Aneurysmal subarachnoid hemorrhage (aSAH) is caused by abnormal blood vessel dilation and subsequent rupture, resulting in blood pooling in the subarachnoid space. This neurological insult results in the activation of the inflammasome, a multiprotein complex that processes pro-inflammatory interleukin (IL)-1 cytokines leading to morbidity and mortality. Moreover, increases in inflammasome proteins are associated with clinical deterioration in many neurological diseases. Limited studies have investigated inflammasome protein expression following aSAH. Reliable markers of the inflammatory response associated with aSAH may allow for earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. Here, we investigated whether inflammasome signaling proteins may serve as potential biomarkers of the inflammatory response in aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls and hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of inflammasome signaling proteins and downstream pro-inflammatory cytokines. Protein measurements were carried out using Simple Plex and Single-Molecule Array (Simoa) technology. The area under the curve (AUC) was calculated using receiver operating characteristics (ROCs) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, a Spearman correlation matrix was performed to determine the correlation between inflammasome protein levels and clinical outcome measures. aSAH subjects demonstrated elevated caspase-1, apoptosis-associated speck-like protein with a caspase recruiting domain (ASC), IL-18 and IL-1β levels in serum, and CSF when compared to controls. Each of these proteins was found to be a promising biomarker of inflammation in aSAH in the CSF. In addition, ASC, caspase-1, and IL-1β were found to be promising biomarkers of inflammation in aSAH in serum. Furthermore, we found that elevated levels of inflammasome proteins in serum are useful to predict worse functional outcomes following aSAH. Thus, the determination of inflammasome protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes.
颅内动脉瘤性蛛网膜下腔出血（aSAH）是由血管异常扩张和随后破裂引起的，导致血液在蛛网膜下腔积聚。这种神经损伤导致炎症小体的激活，炎症小体是一种多蛋白复合物，可处理促炎白细胞介素（IL）-1 细胞因子，导致发病率和死亡率。此外，许多神经疾病中炎症小体蛋白的增加与临床恶化相关。有限的研究调查了 aSAH 后炎症小体蛋白的表达。与 aSAH 相关的炎症反应的可靠标志物可能允许更早地发现有并发症风险的患者，并有助于确定新的药理靶点。在这里，我们研究了炎症小体信号蛋白是否可能作为 aSAH 炎症反应的潜在生物标志物。评估了 15 名 aSAH 患者和年龄匹配的健康对照者以及脑积水（CSF）无动脉瘤对照者的血清和脑脊液（CSF）中的炎症小体信号蛋白和下游促炎细胞因子水平。使用 Simple Plex 和单分子阵列（Simoa）技术进行蛋白质测量。使用接收者操作特征（ROCs）计算曲线下面积（AUC），以获取有关生物标志物可靠性、特异性、敏感性、截止值和似然比的信息。此外，进行了 Spearman 相关矩阵分析，以确定炎症小体蛋白水平与临床结局测量之间的相关性。与对照组相比，aSAH 患者的血清和 CSF 中显示出 caspase-1、带有半胱天冬酶募集域的凋亡相关斑点样蛋白（ASC）、IL-18 和 IL-1β水平升高。这些蛋白中的每一种都被认为是 aSAH 中炎症的有前途的生物标志物。此外，ASC、caspase-1 和 IL-1β 被认为是 aSAH 中炎症的有前途的血清生物标志物。此外，我们发现血清中炎症小体蛋白水平升高可用于预测 aSAH 后功能结局更差。因此，在 aSAH 中测定 CSF 和血清中的炎症小体蛋白水平可能被用作 aSAH 中炎症的可靠生物标志物，并在临床上用于监测患者结局。
