Artikel
Radiocarbon birth dating of cerebral arterio-venous malformations
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Veröffentlicht: | 2. Juni 2015 |
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Gliederung
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Objective: The prevailing notion regarding the chronological development of cerebral arterio-venous malformations (AVMs) is that they are congenital lesions, with only little structural turnover or change. Atmospheric tests of nuclear weapons until 1963 produced a global bomb-pulse of 14C that labeled the entire biosphere and produced a chronometer of molecular or protein synthesis from 1955 to the present. Therefore, we endeavored to a) first identify and isolate a permanent structural protein, with low turnover from the wall of human cerebral arteries (CA) and b) isolate and birth date this candidate protein also in cerebral AVMs.
Method: Samples from cadaveric CAs or extra-cerebral arteries (ECAs) as well as ruptured or unruptured cerebral AVMs from patients undergoing surgical treatment were obtained and treated with a pepsin digestion protocol for isolation and purification of collagen type I from the physiological or pathological vessel walls. Additionally, samples were processed with CNBr, collagenase, trypsin and urea to isolate and ultra-purify elastin as a candidate protein. The carbon-14 (14C) bomb-pulse technique was employed to measure the age of purified elastin extracted from cerebral arteries or from AVMs.
Results: A total of 62 CAs, 20 ECAs from individuals with ages ranging from 1month to 100 years and 30 unruptured or ruptured AVMs could be obtained. A representative set of CAs and cerebral AVMs did not yield a meaningful collagen type I. However, all CAs/ECAs (n=50) and the majority of AVMs (n=20) yielded ultra-purified elastin in sufficient amount for further 14C birth dating. The preliminary 14C accelerator mass spectrometry results dated elastin derived from the arteries with a mean age of 14.5 ± 12.6 years (pooled data, n=20), where as elastin derived from AVMs was less than 5 years old (n=3).
Conclusions: We identified and isolated a durable biomolecule from physiological or pathological CAs for further 14C birth dating. Our data provides the first chronological evidence for the longevity of elastin in CAs and evidence of slow turnover of vascular elastin, as evident based on the inclusion of bomb carbon in elastin from subjects who reached maturity prior to 1955. However, our preliminary data suggests that elastin isolated from cerebral AVMs is contemporary and likely immature. This indicates a deficient structural composition of vessel walls in AVMs and ultimately challenges the concept that AVMs are present for decades.