Loss of mural cells leads to wall degeneration, aneurysm growth, and eventual rupture in a rat aneurysm model.
OBJECTIVE
The biological mechanisms predisposing intracranial saccular aneurysms to growth and rupture are not yet fully understood. Mural cell loss is a histological hallmark of ruptured cerebral aneurysms. It remains unclear whether mural cell loss predisposes to aneurysm growth and eventual rupture.


METHODS
Sodium dodecyl sulfate decellularized and nondecellularized saccular aneurysm from syngeneic thoracic aortas were transplanted to the abdominal aorta of Wistar rats. Aneurysm patency and growth was followed up for 1 month with contrast-enhanced serial magnetic resonance angiographies. Endoscopy and histology of the aneurysms were used to assess the role of periadventitial environment, aneurysm wall, and thrombus remodeling.


RESULTS
Nondecellularized aneurysms (n=12) showed a linear course of thrombosis and remained stable. Decellularized aneurysms (n=12) exhibited a heterogeneous pattern of thrombosis, thrombus recanalization, and growth. Three of the growing aneurysms (n=5) ruptured during the observation period. Growing and ruptured aneurysms demonstrated marked adventitial fibrosis and inflammation, complete wall disruption, and increased neutrophil accumulation in unorganized intraluminal thrombus.


CONCLUSIONS
In the presented experimental setting, complete loss of mural cells acts as a driving force for aneurysm growth and rupture. The findings suggest that aneurysms missing mural cells are incapable to organize a luminal thrombus, leading to recanalization, increased inflammatory reaction, severe wall degeneration, and eventual rupture.
From the Neurosurgery Research Group, Biomedicum Helsinki and Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland (S.M., J.M., K.B., P.H., J.H., M.N., J.F.); Institute of Pathology Länggasse, Bern, Switzerland (M.v.G.); and Experimental MRI Laboratory, Department of Neurology, Helsinki University Central Hospital and Institute of Biomedicine, University of Helsinki, Helsinki, Finland (U.A.-R.).
Serge
S
Marbacher
Johan
J
Marjamaa
Katerina
K
Bradacova
Michael
M
von Gunten
Petri
P
Honkanen
Usama
U
Abo-Ramadan
Juha
J
Hernesniemi
Mika
M
Niemelä
Juhana
J
Frösen
D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology* / Q000637:transplantation; D001014:Aortic Aneurysm / Q000473:pathology*; D001019:Aortic Rupture / Q000473:pathology; D002533:Cerebral Angiography; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D018450:Disease Progression; D004724:Endoscopy; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000637:transplantation; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D016612:Paraffin Embedding; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D013927:Thrombosis / Q000473:pathology
D013501:Surface-Active Agents; D012967:Sodium Dodecyl Sulfate
aneurysm rupture; degeneration; inflammation; intracranial aneurysm; smooth muscle cells; thrombosis