Complement activation associates with saccular cerebral artery aneurysm wall degeneration and rupture.
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.


CONCLUSIONS
These data suggests that complement activation and MAC formation are involved in SCAA wall degeneration and rupture.
Tulamo
Riikka
R
Neurosurgery Research Group, Room B408a2, Biomedicum Helsinki, P.O. Box 700, FI-00029 Huch, Finland. riikka.tulamo@hus.fi
Frösen
Juhana
J
Junnikkala
Sami
S
Paetau
Anders
A
Pitkäniemi
Janne
J
Kangasniemi
Marko
M
Niemelä
Mika
M
Jääskeläinen
Juha
J
Jokitalo
Eija
E
Karatas
Ayse
A
Hernesniemi
Juha
J
Meri
Seppo
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002539:Cerebral Arterial Diseases / Q000276:immunology* / Q000473:pathology*; D003167:Complement Activation / Q000276:immunology*; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013223:Statistics as Topic