Surgery Versus Endovascular Treatment for Proximal Anterior Cerebral Artery Aneurysms: A Meta-Analysis.

BACKGROUND: Proximal anterior cerebral artery (PACA) aneurysms account for less than 1% of all intracranial aneurysms. These aneurysms possess a challenge to surgeons due to their small size, wide base, fragile wall, and accompanying vascular anomalies. Surgery and endovascular treatment are both effective treatment options for PACA aneurysms but there is currently no consensus on which is the method of choice. OBJECTIVE: A systematic review and meta-analysis was conducted to investigate treatment strategies for aneurysms at proximal anterior cerebral artery. MATERIAL AND METHODS: The Cochrane Library, EMBASE, PubMed, and Web of Science databases were systematically searched for studies published between January 01, 2000 and December 01, 2020 that investigated surgery and/or endovascular treatment for patients with PACA. RESULTS AND CONCLUSIONS: Nineteen retrospective studies involving 358 patients met the inclusion criteria. Among these patients, 150 were treated surgically and 208 were treated using an endovascular technique. Preoperative morbidity was significantly greater in the surgical patients compared with the endovascular treated patients but there was no difference between groups in procedural related morbidity. The rates of favorable clinical outcome at time of discharge and at follow-up were statistically significantly greater in the endovascular group compared with the surgical group. Procedural related mortality was 8.7% for the surgical group and 1% in the endovascular group. In summary, our meta-analysis emphasized the safety and efficiency of endovascular treatment, and concluded that it was superior to surgery in acquiring favorable clinical outcome and reducing the perioperative complications. However, surgery was still the preferred treatment strategy for ruptured PACA aneurysms. Preoperative evaluation seems to be of great vital.

Posterior division of ipsilateral C7 transfer to C5 for shoulder abduction limitation.

Background: Reparation of C5 by proximal selective ipsilateral C7 transfer has been reported for the treatment of neurogenic shoulder abduction limitation as an alternative to the reparation of the suprascapular nerve (SSN) and the axillary nerve (AXN) by distal nerve transfers. However, there is a lack of evidence to support either strategy leading to better outcomes based on long-term follow-up. Objective: The purpose of the study was to investigate the safety and long-term outcomes of the posterior division of ipsilateral C7 (PDIC7) transfer to C5 in treating neurogenic shoulder abduction limitation. Methods: A total of 27 cases with limited shoulder abduction caused by C5 injury (24 cases of trauma, 2 cases of neuritis, and 1 case of iatrogenic injury) underwent PDIC7 transfer to the C5 root. A total of 12 cases (11 cases of trauma and 1 case of neuritis) of C5 injury underwent spinal accessory nerve (SAN) transfer to SSN plus the triceps muscular branch of the radial nerve (TMBRN) transfer to AXN. The patients were followed up for at least 12 months for muscle strength and shoulder abduction range of motion (ROM). Results: In cases that underwent PDIC7 transfer, the average shoulder abduction was 105.9° at the 12-month follow-up. In total, 26 of 27 patients recovered at least M3 (13 reached M4) (Medical Research Council Grading) of the deltoid. In cases that underwent SAN transfer to SSN plus TMBRN to AXN, the average shoulder abduction was 84.6° at the 12-month follow-up. In total, 11 of 12 patients recovered at least M3 (4 reached M4) of the deltoid. Conclusion: Posterior division of ipsilateral C7 transfer is a one-stage, safe, and effective surgical procedure for patients with neurogenic shoulder abduction limitation.

Ablation of NLRP3 inflammasome attenuates muscle atrophy via inhibiting pyroptosis, proteolysis and apoptosis following denervation.

Rationale: The inflammasome has been widely reported to be involved in various myopathies, but little is known about its role in denervated muscle. Here, we explored the role of NLRP3 inflammasome activation in experimental models of denervation in vitro and in vivo. Methods: Employing muscular NLRP3 specific knock-out (NLRP3 cKO) mice, we evaluated the effects of the NLRP3 inflammasome on muscle atrophy in vivo in muscle-specific NLRP3 conditional knockout (cKO) mice subjected to sciatic nerve transection and in vitro in cells incubated with NLRP3 inflammasome activator (NIA). To evaluate the underlying mechanisms, samples were collected at different time points for RNA-sequencing (RNA-seq), and the interacting molecules were comprehensively analysed. Results : In the experimental model, NLRP3 inflammasome activation after denervation led to pyroptosis and upregulation of MuRF1 and Atrogin-1 expression, facilitating ubiquitin-proteasome system (UPS) activation, which was responsible for muscle proteolysis. Conversely, genetic knockout of NLRP3 in muscle inhibited pyroptosis-associated protein expression and significantly ameliorated muscle atrophy. Furthermore, cotreatment with shRNA-NLRP3 markedly attenuated NIA-induced C2C12 myotube pyroptosis and atrophy. Intriguingly, inhibition of NLRP3 inflammasome activation significantly suppressed apoptosis. Conclusions: These in vivo and in vitro findings demonstrate that during denervation, the NLRP3 inflammasome is activated and stimulates muscle atrophy via pyroptosis, proteolysis and apoptosis, suggesting that it may contribute to the pathogenesis of neuromuscular diseases.

Molecular feature of neutrophils in immune microenvironment of muscle atrophy.

Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as ageing, disuse and denervation, tip the balance and induce skeletal muscle atrophy. Skeletal muscle atrophy, which involves complex physiological and biochemical changes, is accompanied by adverse outcomes and even increased mortality. Multiple studies have investigated the role of neutrophils in atrophied skeletal muscles; however, neutrophil intrusion in muscle is still a polemical knot. As technical obstacles have been overcome, people have gradually discovered new functions of neutrophils. The classical view of neutrophils is no longer applicable to their biological characteristics. To date, no clear association between the hidden injurious effect of neutrophil intrusion and muscle atrophy has been convincingly proven. Throughout this review, we have discussed the neutrophil activities that mediate muscle atrophy for distinct disease occurrences. Hopefully, this review will help both clinicians and researchers of skeletal muscle atrophy with relevant targets to further explore efficient medical interventions and treatments.

ROS-activated CXCR2+ neutrophils recruited by CXCL1 delay denervated skeletal muscle atrophy and undergo P53-mediated apoptosis.

Neutrophils are the earliest master inflammatory regulator cells recruited to target tissues after direct infection or injury. Although inflammatory factors are present in muscle that has been indirectly disturbed by peripheral nerve injury, whether neutrophils are present and play a role in the associated inflammatory process remains unclear. Here, intravital imaging analysis using spinning-disk confocal intravital microscopy was employed to dynamically identify neutrophils in denervated muscle. Slice digital scanning and 3D-view reconstruction analyses demonstrated that neutrophils escape from vessels and migrate into denervated muscle tissue. Analyses using reactive oxygen species (ROS) inhibitors and flow cytometry demonstrated that enhanced ROS activate neutrophils after denervation. Transcriptome analysis revealed that the vast majority of neutrophils in denervated muscle were of the CXCR2 subtype and were recruited by CXCL1. Most of these cells gradually disappeared within 1 week via P53-mediated apoptosis. Experiments using specific blockers confirmed that neutrophils slow the process of denervated muscle atrophy. Collectively, these results indicate that activated neutrophils are recruited via chemotaxis to muscle tissue that has been indirectly damaged by denervation, where they function in delaying atrophy.

Oxidative stress-induced premature senescence and aggravated denervated skeletal muscular atrophy by regulating progerin-p53 interaction.

BACKGROUND: Progerin elevates atrophic gene expression and helps modify the nuclear membrane to cause severe muscle pathology, which is similar to muscle weakness in the elderly, to alter the development and function of the skeletal muscles. Stress-induced premature senescence (SIPS), a state of cell growth arrest owing to such stimuli as oxidation, can be caused by progerin. However, evidence for whether SIPS-induced progerin accumulation is connected to denervation-induced muscle atrophy is not sufficient. METHODS: Flow cytometry and a reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) inhibitors were used to assess the effect of oxidation on protein (p53), progerin, and nuclear progerin-p53 interaction in the denervated muscles of models of mice suffering from sciatic injury. Loss-of-function approach with the targeted deletion of p53 was used to assess connection among SIPS, denervated muscle atrophy, and fibrogenesis. RESULTS: The augmentation of ROS and iNOS-derived NO in the denervated muscles of models of mice suffering from sciatic injury upregulates p53 and progerin. The abnormal accumulation of progerin in the nuclear membrane as well as the activation of nuclear progerin-p53 interaction triggered premature senescence in the denervated muscle cells of mice. The p53-dependent SIPS in denervated muscles contributes to their atrophy and fibrogenesis. CONCLUSION: Oxidative stress-triggered premature senescence via nuclear progerin-p53 interaction that promotes denervated skeletal muscular atrophy and fibrogenesis.

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.

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.

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.

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.