Tulamo Riikka, Frösen Juhana, Junnikkala Sami, Paetau Anders, Pitkäniemi Janne, Kangasniemi Marko, Niemelä Mika, Jääskeläinen Juha, Jokitalo Eija, Karatas Ayse, Hernesniemi Juha, Meri Seppo
Neurosurgery Research Group, Room B408a2, Biomedicum Helsinki, P.O. Box 700, FI-00029 Huch, Finland.
Neurosurgery. 2006 Nov;59(5):1069-76; discussion 1076-7. doi: 10.1227/01.NEU.0000245598.84698.26.
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.
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.
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.
These data suggests that complement activation and MAC formation are involved in SCAA wall degeneration and rupture.
囊状脑动脉动脉瘤（SCAA）壁退变和炎性细胞浸润与动脉瘤破裂及蛛网膜下腔出血相关，可导致一种毁灭性的中风形式。补体系统是炎症及受损组织修复过程中的关键介质。我们研究了补体激活与SCAA壁退变和破裂之间的关系，以更好地理解SCAA壁破裂的病理生物学机制。
对显微手术夹闭后切除的未破裂（n = 26）和破裂（n = 32）的SCAA底部进行研究，通过免疫染色检测补体激活（膜攻击复合物[MAC]），并通过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检测相关细胞死亡。补体激活与临床及其他组织学参数相关。采用电子显微镜和免疫电子显微镜在超微结构水平定位MAC沉积。
MAC始终定位于SCAA外壁的无细胞层，且在所有SCAA样本中均有发现。相对于SCAA壁总面积，MAC阳性面积的百分比（范围为5 - 77%）在破裂的SCAA（n = 25；中位数为39%）中高于未破裂的SCAA（n = 18；中位数为20%；P = 0.005）。它还与SCAA壁退变（P < 0.001）、去内皮化（P < 0.001）以及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个双重染色样本中的4个样本中，凋亡的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阳性细胞核和MAC位于同一壁区域，但未发现双阳性细胞。对一个未破裂的SCAA进行电子显微镜和免疫电子显微镜检查显示，SCAA外壁MAC阳性层存在细胞死亡。
这些数据表明补体激活和MAC形成参与了SCAA壁退变和破裂。
