Safety and efficacy of different therapeutic strategies in the endovascular treatment of anterior cerebral artery aneurysms with different features: A single centre experience.

BACKGROUND: Outcomes of endovascular treatment of anterior cerebral artery (ACA) aneurysms are still not well-characterized. OBJECTIVE: The study aimed to review the clinical effect, procedure-related complications and follow-up outcomes and to evaluate the safety and efficacy of endovascular treatment of ACA aneurysms in our center experience. METHODS: From August 2014 to August 2018, a total of 75 consecutive patients with 77 ACA aneurysms were treated via the endovascular approach after providing informed consent. A retrospective review of the clinical, radiological, and endovascular details of these patients was conducted. RESULTS: The mortality and the morbidity in this study were 4% and 9.3%, respectively. Compared with A1 and A2 aneurysms, intraoperative rupture was more common in A3 aneurysms (P = 0.029). Difference between the ruptured and unruptured aneurysms in the distribution of therapeutic strategy (P = 0.003) and immediate embolization degree (P = 0.004) was also significant. Statistical analysis demonstrated that the larger aneurysm (P = 0.031) was, the greater the ratio of aneurysm size to parent artery diameter (P = 0.029) was, the more likely the unruptured aneurysms were to occur ischemic events. Higher Hunt-Hess grade (P = 0.0066) was an independent risk factor for poor clinical outcome. CONCLUSION: Endovascular treatment is feasible and effective for ACA aneurysms.

Inhibition of AIM2 inflammasome activation alleviates GSDMD-induced pyroptosis in early brain injury after subarachnoid haemorrhage.

Only a few types of inflammasomes have been described in central nervous system cells. Among these, the absent in melanoma 2 (AIM2) inflammasome is primarily found in neurons, is highly specific and can be activated only by double-stranded DNA. Although it has been demonstrated that the AIM2 inflammasome is activated by poly(deoxyadenylic-deoxythymidylic) acid sodium salt and leads to pyroptotic neuronal cell death, the role of AIM2 inflammasome-mediated pyroptosis in early brain injury (EBI) after subarachnoid haemorrhage (SAH) has rarely been studied. Thus, we designed this study to explore the mechanism of gasdermin D(GSDMD)-induced pyroptosis mediated by the AIM2 inflammasome in EBI after SAH. The level of AIM2 from the cerebrospinal fluid (CSF) of patients with SAH was detected. The pathway of AIM2 inflammasome-mediated pyroptosis, the AIM2/Caspase-1/GSDMD pathway, was explored after experimental SAH in vivo and in primary cortical neurons stimulated by oxyhaemoglobin (oxyHb) in vitro. Then, we evaluated GSDMD-induced pyroptosis mediated by the AIM2 inflammasome in AIM2 and caspase-1- deficient mice and primary cortical neurons generated through lentivirus (LV) knockdown. Compared with that of the control samples, the AIM2 level in the CSF of the patients with SAH was significantly increased. Pyroptosis-associated proteins mediated by the AIM2 inflammasome were significantly increased in vivo and in vitro following experimentally induced SAH. After AIM2 and caspase-1 were knocked down by an LV, GSDMD-induced pyroptosis mediated by the AIM2 inflammasome was alleviated in EBI after SAH. Intriguingly, when caspase-1 was knocked down, apoptosis was significantly suppressed via impeding the activation of caspase-3. GSDMD-induced pyroptosis mediated by the AIM2 inflammasome may be involved in EBI following SAH. The inhibition of AIM2 inflammasome activation caused by knocking down AIM2 and caspase-1 alleviates GSDMD-induced pyroptosis in EBI after SAH.

Morphology parameters for rupture in middle cerebral artery mirror aneurysms.

OBJECTIVE: To identify the morphological parameters correlated with the rupture of middle cerebral artery (MCA) aneurysms. METHODS: We retrospectively analyzed the digital subtraction angiography (DSA) data of 48 patients with ruptured mirror MCA aneurysms. Morphological parameters included aneurysm with wall protrusion, maximum diameter (Dmax), height, neck width, aneurysm width, dome projection, parent artery average diameter (Dp), aspect ratio (AR), bottleneck factor (BNF), size ratio (SR), M1/M2 ratio, and height/width (H/W) ratio. These paired parameters were analyzed by conditional univariate and multivariate logistic regressions to screen out the independent risk factors. We established a score based on the independent risk factors. Receiver operating characteristics (ROC) were generated to estimate the prediction performance of the score in our large database of 763 aneurysms. RESULTS: In the univariate regressions, Dmax, height, aneurysm width, neck width, AR, BNF, H/W ratio, SR, anterior dome projection and aneurysm with wall protrusion were significant risk factors. Aneurysm width (OR 3.296, p=0.015), AR (OR 11.594, p=0.014) and anterior dome projection (OR 9.385, p=0.016) were independent risk factors in multivariate regression. The area under the curve (AUC) value of the score based on the three independent risk factors was 0.829. CONCLUSION: Aneurysm width, AR and anterior dome projection were independent risks factors of rupture.

Receptor-Mediated Delivery of Astaxanthin-Loaded Nanoparticles to Neurons: An Enhanced Potential for Subarachnoid Hemorrhage Treatment.

Astaxanthin (ATX) is a carotenoid that exerts strong anti-oxidant and anti-inflammatory property deriving from its highly unsaturated molecular structures. However, the low stability and solubility of ATX results in poor bioavailability, which markedly hampers its application as therapeutic agent in clinic advancement. This study investigated a promising way of transferrin conjugated to poly (ethylene glycol) (PEG)-encapsulated ATX nanoparticles (ATX-NPs) on targeted delivery and evaluated the possible mechanism underlying neuroprotection capability. As a result, the ATX integrated into nanocarrier presented both well water-dispersible and biocompatible, primely conquering its limitations. More than that, the transferrin-containing ATX-NPs exhibited enhanced cellular uptake efficiency than that of ATX-NPs without transferrin conjugated in primary cortical neurons. Additionally, compared to free ATX, transferrin-containing ATX-NPs with lower ATX concentration showed powerful neuroprotective effects on OxyHb-induced neuronal damage. Taken together, the improved bioavailability and enhanced neuroprotective effects enabled ATX-NPs as favorable candidates for targeted delivery and absorption of ATX. We believe that these in vitro findings will provide insights for advancement of subarachnoid hemorrhage therapy.