Loci minoris resistiae of the cerebral arterial network

In our study, the presence of a single unruptured sIA did not influence the rupture pressure values ​​of specific AC segments. Moreover, the bifurcation regions exhibited high strength and the fracture pressure did not differ significantly depending on the fracture location of the analyzed CAs, especially at the wall or the bifurcation region. Nevertheless, based on Mitchell and Jakubowski’s study, the mean rupture pressure of branched CA specimens was significantly lower than the rupture pressure of straight CA specimens.¹². Alternatively, Ciszek et al. did not observe a significant difference in burst pressure values ​​between straight and branched CA specimens¹³. In our study, the rupture most often occurred at the level of the wall of the CAs analyzed. During pressure-inflation testing, the bifurcation region ruptured in 40% of MCAs in the aneurysm group and in 25% of MCAs and 12.5% ​​of ACIs in the non-aneurysm group. However, such a high strength of CA bifurcations may be counterintuitive considering that the bifurcation regions are histologically characterized by a discontinuity in the middle.¹⁴ and enlarged fenestrations in the internal elastic blade⁴. Finlay et al. reported that the arrangement of adventitial collagen fibers at the apex of the bifurcation differs from that of the right arterial segments. In the bifurcation region, the collagen fibers are densely co-aligned and form a strong tendon-like band that provides high resistance to AC bifurcation¹⁵.

The development of sIA comprises a sequence of overlapping adaptive and degenerative processes induced by specific hemodynamic factors. It is only when the degenerative processes prevail over the adaptive processes that the wall strength decreases, leading to a rupture of sIA⁹. Thus, not all sIAs correspond to regions of low wall resistance. In a study by Ciszek et al., one sIA ruptured under pressure significantly exceeding physiological blood pressure, while another sIA maintained elevated intraluminal pressure values¹³. Additionally, during the experiments conducted by Mitchell and Jakubowski, the sIA sample was pressurized up to 1.6 bar (1200 mmHg) and rupture occurred in the wall of the adjacent AC.¹². Similarly, in our study, none of the analyzed sIAs ruptured at physiological pressures. Moreover, in the case of five sIA specimens, the failure occurred away from the sIA, indicating its high wall strength. According to the Finnish Lifetime Cohort Follow-up Study, about 70% of AVS did not rupture during lifetime observation¹⁶ which is consistent with the results of our study, as well as the pressure-inflation test studies of CAs mentioned above.

Specific CA segments, particularly ACommA, that are prone to sIA formation simultaneously predispose to an increased risk of sIA rupture. In a retrospective epidemiological study by Carter et al., ruptured AVS were most often localized to the ACommA complex. In addition, the average size of sIAs involving the ACommA or distal branches of major ACs was smaller than that of sIAs observed in large ACs, such as the bifurcation of the ICA or MCA. Carter et al. hypothesized that there is a decrease in sIA wall thickness with a decrease in parent artery caliber¹⁷. It may be reasonable to consider Laplace’s law applied to this context: assuming similar pressure conditions and the same diameter, thin-walled IAs experience remarkably higher intramural stresses than their thick-walled counterparts. Similarly, in our study, ACommA exhibited a significantly lower mean rupture pressure than the ICA and MCA bifurcation in the aneurysm and non-aneurysm groups. Additionally, CAs of smaller diameter and length were characterized by lower burst pressure values. However, in a study by Ciszek et al., as well as in a study by Mitchell and Jakubowski, the authors did not observe significant differences between the values ​​of rupture pressure depending on the location of the CA segment.^12.13. Further investigations, including histological studies with wall thickness measurement, are needed to clarify the relationship between CA caliber and their wall strength.

CA mechanobiology

CA burst pressure values ​​in both groups analyzed significantly exceeded the maximum arterial pressure in vivo¹⁸ which is consistent with previous CA pressure-inflation test results. In a study by Mitchell and Jakubowski, the average burst pressure of all CAs analyzed was 1.848 bar (1386 mmHg), while the average burst pressure of CAs presented in a study by Ciszek et al. was 2.35 atm (1786 mmHg)^12.13. Such discrepancies in literature data regarding burst pressure values ​​may result from the diverse age distribution of AC donors. The mean age at death of autopsy subjects was 69 years in the first study and 47 years in the second study. Moreover, both studies revealed a significant negative dependence of CA burst pressure with age. Thus, the relatively higher average CA burst pressure obtained by Ciszek et al. can be explained by the predominance of AC taken from younger autopsy subjects.

The progressive decrease in AC bursting pressure with age, similar to the progressive increase with age in AC stiffness, may be attributable to age-related arterial wall remodeling, including degeneration internal elastic lamina⁵. Specifically, elastin is the main load-bearing material under low-stress conditions, while collagen fibers maintain the structural integrity of CA under further increase in mechanical loads. Progressive elastin degradation leads to an age-related increase in AC stiffness at low stress regimes, indicating early recruitment of collagen fibers. Since collagen fibers are capable of slight deformations before rupture, once elastin function is impaired, the intramural stress in the AC wall increases under the same pressure conditions.¹⁹. Nevertheless, in case of samples composed mainly of collagen, separated CA weeds, the negative association between the values ​​of rupture pressure and age was also observed.²⁰. This can be explained by the stiffening of collagen fibers during aging. According to the study by Wuyts et al. transition stress, i.e. the stress at which collagen fibers are involved in the mechanical response, decreases with age²¹. Therefore, it can be assumed that a significant decrease in burst pressure values ​​with age exclusively in CAs of the aneurysm group indicates a more pronounced progression of elastin degradation and collagen stiffening in the arterial wall. compared to CAs in the non-aneurysm group. However, we did not find a significant difference between the experimental and control groups in terms of mean CA bursting pressure. This discrepancy may be explained by the narrowness of the age distribution of CA donors. If the ACs of the younger and older autopsy subjects had been pressurized, then the ACs of the non-aneurysm group may have exhibited a similar negative dependence of bursting pressure with age.