Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture
Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture
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DOI：
10.1227/01.neu.0000245598.84698.26
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发表时间：
2006-11-01
期刊：
影响因子：
4.8
通讯作者：
Meri, Seppo
中科院分区：
文献类型：
--
作者：
Tulamo, Riikka;Frosen, Juhana;Meri, Seppo
目的：脑囊性动脉瘤（SCAA）壁变性和炎症细胞浸润与动脉瘤破裂和蛛网膜下腔出血有关，导致一种毁灭性的中风形式。补体系统是炎症和损伤组织处理的关键中介。我们研究了补体活化与SCAA壁变性和破裂的关系，以更好地了解SCAA壁破裂的病理生物学。方法：采用补体活化免疫染色（膜攻击复合体[MAC]）和末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记反应研究显微手术夹断后切除的未破裂（n = 26）和破裂（n = 32）的SCAA基底。补体活化与临床及其他组织学参数相关。利用电镜和免疫电镜对MAC沉积进行超微结构定位。结果：MAC一致地定位于SCAA外壁的脱细胞层，并且在所有SCAA样品中都有发现。破裂的SCAA （n = 25，中位数，39%）比未破裂的SCAA （n = 18，中位数，20%,P = 0.005）中mac阳性面积相对于总SCAA壁表面积的百分比（范围，5-77%）更大。它还与SCAA壁变性（P < 0.001）、去内皮化（P < 0.001）、CD163（+）巨噬细胞（P = 0.023）和t淋巴细胞（P = 0.030）浸润显著相关。在14个双染色样本中，4个细胞的凋亡末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口端标记阳性细胞核和MAC位于相同的细胞壁区域，但未发现双阳性细胞。电镜和免疫电镜显示未破裂的SCAA外壁mac阳性层细胞死亡。结论：这些数据提示补体激活和MAC的形成参与了SCAA壁的变性和破裂。
OBJECTIVE: Saccular cerebral artery aneurysm (SCAA) wall degeneration and inflammatory cell infiltrations associate with aneurysm rupture and subarachnoid hemorrhage, resulting in a devastating form of stroke. The complement system is the key mediator of inflammation and household processing of injured tissue. We studied how complement activation associates with SCAA wall degeneration and rupture to better understand the pathobiology of SCAA wall rupture.METHODS: Unruptured (n = 26) and ruptured (n = 32) SCAA fundi resected after microsurgical clipping were studied by immunostaining for complement activation (membrane attack complex [MAC]) and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling reaction for related cell death. Complement activation was correlated with clinical and other histological parameters. Electromicroscopy and immunoelectron microscopy were used for locating MAC depositions at the ultrastructural level.RESULTS: MAC localized consistently in a decellularized layer in the outer SCAA wall, and was found in all SCAA samples. The percentage of MAC-positive area relative to the total SCAA wall surface area (range, 5-77%) was greater in ruptured (n = 25; median, 39%) than in unruptured SCAAs (n = 18; median, 20%; P = 0.005). It also associated significantly with SCAA wall degeneration (P < 0.001), de-endothelialization (P < 0.001), and CD163(+) macrophage (P = 0.023) and T-lymphocyte (P = 0.030) infiltrations. Apoptotic terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling-positive nuclei and MAC were located at the same wall areas in four out of 14 double-stained samples, but no double-positive cells were found. Electromicroscopy and immunoelectron microscopy of an unruptured SCAA showed cell death in the MAC-positive layers in the outer SCAA wall.CONCLUSION: These data suggests that complement activation and MAC formation are involved in SCAA wall degeneration and rupture.