Introduction: The chronological development of brain arteriovenous malformations (AVM) is controversial. Atmospheric nuclear testing until 1963 produced a global bomb-pulse of 14C and thus a chronometer of molecular synthesis in the entire biosphere from 1955 to the present. We isolated and dated a durable, representative structural protein from human cerebral arteries (CA) and brain AVMs.
Method: Samples from cadaveric CAs or from brain AVMs from patients undergoing surgical resection were processed to ultra- purify elastin. The age of purified elastin extracted from cerebral arteries or from AVMs was measured using 14C bomb-pulse technique. We modified a 14C biological incorporation equation model using variable AVM formation dates and elastin formation and degradation rates.
Results: A total of 62 CAs from individuals with ages ranging from 1 month to 100 years and 30 unruptured or ruptured AVMs were collected. All CAs and nearly all AVMs yielded ultra-purified elastin in sufficient amount for further 14C birth dating. Mean age of elastin was 13.4± 11.2 years (n = 34), whereas elastin derived from AVMs was less than 5 years old (n = 15, p = 0.002). Based on 14C content relative subject birthdate and date of tissue collection, best-fit modeling of CA and AVM elastin demonstrated turnover rates less than 2% and 25 - 50%, respectively. Amongst AVMs, those with associated aneurysms had younger elastin (p=0.007). Larger AVMs tended to have younger elastin (p=0.086) and AVM rupture was not associated with elastin age (p=0.358).
Conclusions: Our data provides the first chronological evidence for the longevity of elastin in CAs, as evident based on the inclusion of bomb carbon in elastin from subjects who reached maturity prior to 1955. Importantly it also demonstrates elastin isolated from brain AVMs is contemporary and likely immature suggesting a non-congenital origin and/or rapid vascular turnover.