Marklund Niklas, Zolfaghari Shaian, Westerberg Gustaf, Ruscher Karsten, Englund Elisabet, Redebrandt Henrietta Nittby
Department of Clinical Sciences Lund, Division of Neurosurgery, Department of Neurosurgery, Lund University and Skane University Hospital, Lund, Sweden.
Department of Clinical Science, Division of Pathology, Lund University, Lund, Sweden.
Inflammation. 2024 Dec 9. doi: 10.1007/s10753-024-02210-3.
Emerging data suggest a complex pathophysiology of chronic subdural hematoma (CSDH) to which an inflammatory response might contribute. The complement system is activated in acute traumatic setting, although its role in CSDH is unknown. To investigate the complement system in CSDH pathophysiology, we analyzed blood and hematoma fluid biomarkers, as well as immunohistochemistry of the CSDH membrane and dura.
We simultaneously collected CSDH fluid and peripheral blood from 20 CSDH patients at the time of surgery. Biopsies of the dura mater and the CSDH capsule were obtained and analyzed by immunohistochemistry for C5b-C9 or C5a deposition. Biomarkers of inflammation and complement activation were analyzed by a 21-multiplex assay, including Adiponectin, Clusterin, Complement factor C9 and CRP. Complement factor C5a was analyzed separately by a commercial R-plex electrochemiluminescence assay.
Ten biomarkers differed significantly between peripheral blood and paired CSDH of which two were significantly increased in CSDH fluid (Clusterin and Cystatin C). Eight of the significantly altered biomarkers were significantly decreased in CSDH fluid, including C5a, Complement 9 and Adiponectin. There was no immunoreactivity for C5a or the C5b-C9 membrane attack complex in the dura or CSDH membrane.
In CSDH levels of the complement inhibitor Clusterin were increased, whereas levels of C5a and C9 were decreased. Membrane attack complex C5b-C9 was not detected in the membrane or dura surrounding the CSDH. Inhibition of complement could lead to reduced clearance of debris in the CSDH as well as secondary inflammatory reactions.
新出现的数据表明慢性硬膜下血肿(CSDH)的病理生理过程复杂,炎症反应可能参与其中。补体系统在急性创伤情况下被激活,但其在CSDH中的作用尚不清楚。为了研究补体系统在CSDH病理生理过程中的作用,我们分析了血液和血肿液中的生物标志物,以及CSDH包膜和硬脑膜的免疫组化情况。
我们在手术时同时收集了20例CSDH患者的CSDH液和外周血。获取硬脑膜和CSDH包膜的活检组织,通过免疫组化分析C5b - C9或C5a的沉积情况。通过21重检测法分析炎症和补体激活的生物标志物,包括脂联素、簇集素、补体因子C9和C反应蛋白。补体因子C5a通过商业R - plex电化学发光检测法单独分析。
外周血和配对的CSDH之间有10种生物标志物存在显著差异,其中两种在CSDH液中显著升高(簇集素和胱抑素C)。8种显著改变的生物标志物在CSDH液中显著降低,包括C5a、补体9和脂联素。硬脑膜或CSDH包膜中未检测到C5a或C5b - C9膜攻击复合物的免疫反应性。
在CSDH中,补体抑制剂簇集素水平升高,而C5a和C9水平降低。在CSDH周围的包膜或硬脑膜中未检测到膜攻击复合物C5b - C9。补体抑制可能导致CSDH中碎片清除减少以及继发性炎症反应。