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Background and Purpose: Endovascular aneurysm treatment relies on a biological process, including cell migration for thrombus organization and growth of a neointima. To better understand aneurysm healing, our study explores the origin of neointima-forming and thrombus-organizing cells in a rat saccular sidewall aneurysm model. Methods: Saccular aneurysms were transplanted onto the abdominal aorta of male Lewis rats and endovascularly treated with coils (n=28) or stents (n=26). In 34 cases, GFP+ (green fluorescent protein)-expressing vital aneurysms were sutured on wild-type rats, and in 23 cases, decellularized wild-type aneurysms were sutured on GFP+ rats. Follow-up at 3, 7, 14, 21, and 28 days evaluated aneurysms by fluorescence angiography, macroscopic inspection, and microscopy for healing and inflammation status. Furthermore, the origin of cells was tracked with fluorescence histology. Results: In animals with successful functional healing, histological studies showed a gradually advancing thrombus organization over time characterized by progressively growing neointima from the periphery of the aneurysm toward the center. Cell counts revealed similar distributions of GFP+ cells for coil or stent treatment in the aneurysm wall (54.4% versus 48.7%) and inside the thrombus (20.5% versus 20.2%) but significantly more GFP+ cells in the neointima of coiled (27.2 %) than stented aneurysms (10.4%; P =0.008). Conclusions: Neointima formation and thrombus organization are concurrent processes during aneurysm healing. Thrombus-organizing cells originate predominantly in the parent artery. Neointima formation relies more on cell migration from the aneurysm wall in coiled aneurysms but receives greater contributions from cells originating in the parent artery in stent-treated aneurysms. Cell migration, which allows for a continuous endothelial lining along the parent artery’s lumen, may be a prerequisite for complete aneurysm healing after endovascular therapy. In terms of translation into clinical practice, these findings may explain the variability in achieving complete aneurysm healing after coil treatment and the improved healing rate in stent-assisted coiling.

Background and purposeDespite significant technical advances, recanalization rates after endovascular therapy of ruptured intracranial aneurysms (IAs) remain a clinical challenge. A histopathological hallmark of ruptured human IA walls is mural cell loss. Mural smooth muscle cells (SMCs) are known to promote intraluminal healing in thrombosed experimental aneurysms. In this rat model we assess the natural history and healing process after coil embolization in SMC-rich and decellularized aneurysms.MethodsSaccular aneurysms were created by end-to-side anastomosis of an arterial graft from the descending thoracic aorta of a syngeneic donor rat to the infrarenal abdominal aorta of recipient male Wistar rats. Untreated arterial grafts were immediately transplanted, whereas aneurysms with loss of mural cells were chemically decellularized before implantation. Aneurysms underwent coil implantation during aneurysm anastomosis. Animals were randomly assigned either to the non-decellularized or decellularized group and underwent macroscopic and histological analyses on days 3, 7, 21, or 90 post-coil implantation.ResultsA total of 55 rats underwent macroscopic and histologic analysis. After coil embolization, aneurysms with SMC-rich walls showed a linear course of thrombosis and neointima formation whereas decellularized aneurysms showed marked inflammatory wall degeneration with increased recanalization rates 21 days (p=0.002) and 90 days (p=0.037) later. The SMCs showed the ability to actively migrate into the intra-aneurysmal thrombus and participate in thrombus organization.ConclusionsCoil embolization of aneurysms with highly degenerated walls is prone to further wall degeneration, increased inflammation, and recanalization compared with aneurysms with vital SMC-rich walls.

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th–April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017–2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.

Investigations have shown a multifactorial process as cause for the poor outcome after subarachnoid hemorrhage (SAH), including inflammation, early brain injury, cortical spreading depression, lack of cerebral autoregulation and the cerebral vasospasm (CVS) itself. Losartan may have a beneficial effect after SAH - preventing CVS, restoring cerebral autoregulation, reducing inflammation and early brain injury. Also some data is available for an AT1-receptor-upregulation and upregulated gene expression after subarachnoid hemorrhage, but the functional role of angiotensin on the cerebrovascular contractility is still not completely understood. Therefore, the aim of the present investigation was to detect functional interactions between the AT1-receptor blockade (by losartan) and the endothelin-1 (ET-1) dependent vasoconstriction and vasorelaxation in the basilar artery. To investigate the functional role of losartan on rat's basilar artery, changes of the vasoreactivity in an organ bath were determined. Under losartan the ET-1 induced contraction is decreased. After incubation with BQ-788, an ET(B)-receptor antagonist, the lowered contraction is abolished. In precontracted vessels under losartan and BQ-123, an ET(A)-receptor antagonist, ET-1 induced a higher relaxation. AT1-receptor antagonism causes a modulatory effect in ET(B)-receptor-dependent vasorelaxation in the basilar artery. AT1-receptor antagonism due to losartan induces the upregulation of the NO-pathway with a significantly increased relaxation accompanied with enhanced sensitivity of the ET(B)-receptor. Losartan has a dose-dependent antagonistic effect to the ET-1 induced contraction, which seems to ET(B)-receptor dependent. This antagonistic effect could be another beneficial effect after subarachnoid hemorrhage, additionally to the known effects after stroke: preventing CVS, restoring cerebral autoregulation, reducing inflammation and early brain injury.