The Pathobiology of Saccular Cerebral Artery Aneurysm Rupture and Repair -a Clinicopathological and Experimental Approach

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Review of the literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Figure 1. Saccular cerebral artery aneurysm (SCAA) . . . . . . . . . . . . . . . . . . 13 Figure 2. Subarachnoid hemorrhage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Figure 3. Odds ratios of SAH risk factors and the risk of SAH .....................16 Table 1. Aneurysm (A) and patient (B) related risk factors for subarachnoid hemorrhage . . . . . . . . . . . 16 Figure 4. Histology of extracranial and intracranial arteries . . . . . . . . . . . . 18 Figure 5. Histology of the cerebral arteries . . . . . . . . . . . . . . . . . . . . . . . . . . 19 6.1 Saccular cerebral artery aneurysms (SCAA) and subarachnoid hemorrhage (SAH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 6.1.1 SAH caused by SCAA rupture . . . . . . . . . . . . . . . . . . . . . . . . . 20 6.1.2 Diagnostics of SAH and SCAAs . . . . . . . . . . . . . . . . . . . . . . . 22 6.1.3 Risk factors for SCAA formation and rupture . . . . . . . . . 24 6.1.4 Current therapies to prevent SCAA rupture and subsequent SAH. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 6.1.5 Summary of current problems in the diagnostics and therapy of SCAAs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 6.2 Cellular and molecular pathology of the SCAA wall. . . . . . . . . . . 36 6.2.1 Origin of SCAAs – acquired, not congenital lesions . . . 36 6.2.2 Infection and infl ammation and SCAA formation . . . . . 38 6.2.3 Molecular genetics of SCAAs . . . . . . . . . . . . . . . . . . . . . . . . . . 38 6.2.4 Histology of SCAA walls. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 6.2.5 Mechanisms of SCAA wall degeneration and rupture . . . 42 6.2.6 Adaptation and repair mechanisms of the SCAA wall . . . 50 6.2.7 Summary of the putative cellular and molecular mechanisms of rupture and repair of the SCAA wall. . . 52