gms | German Medical Science

Objective: The natural history of cerebral aneurysms (CAs), especially how long CAs may have existed before clinical presentation, remains incompletely understood and controversial. We used radiocarbon birth dating to measure the age of collagen, which is the main constituent of CAs, as an indicator for biosynthesis and turnover of CAs.

Method: Forty-six CA samples from 43 patients undergoing surgical repair of ruptured or unruptured CAs were obtained. Collagen I was purified from CA samples and 14C levels were measured by accelerator mass spectrometry. The estimated CA collagen ages were correlated with CA rupture status and factors, which have been associated with aneurysm progression and rupture. Collagen extracted from mouse tendons served as controls. Ten intracerebral and 2 extracerebral arteries from human cadavers were used to estimate physiological collagen I-turnover in relation to aneurysms.

Results: Nearly all CA collagen samples were less than 5 years old, irrespective of patient age, CA size, morphology, or rupture status. However, CAs from patients with a history of cardiovascular risk factors, e.g. smoking or hypertension, contained significantly younger collagen, compared to CAs from patients with no risk factors (mean 1.6 ± 1.2 years versus 3.9 ± 3.3 years, respectively, p= 0.012). The collagen samples from mouse tendons confirmed the validity of the method since all of these samples gave F14C values for collagen corresponding to the F14C values of the mouse chow fed to the animals (data not shown). The 12 samples from the human cerebral arteries did not yield substantial amounts of collagens I or V.

Conclusions: Our data indicate that the main constituent of CAs is relatively and consistently young when detected, suggesting that there is ongoing collagen remodeling in CAs, which is accelerated in patients with risk factors. Additionally, the analysis of the human cerebral arteries suggests a distinctly lower biosynthesis and/or turnover of collagens I and V, compared to CAs. Our results challenge the prevailing opinion that CAs can be present for decades and that they only undergo sporadic episodes of structural change. Moreover, our results support modification of risk factors and more frequent follow-up of patients with conservatively managed CAs and concomitant risk factors.