Dimethyl Itaconate Reduces Cognitive Impairment and Neuroinflammation in APPswe/PS1ΔE9 Transgenic Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia characterized by abnormal accumulation of amyloid-ß (Aß) plaques, neuroinflammation, and neuronal loss. Dimethyl itaconate (DI), a membrane-permeable derivative of itaconate, has been recently reported to limit inflammation. However, the effect of DI in the APPswe/PS1ΔE9 (APP/PS1) transgenic mouse model of AD remains unclear. We treated APP/PS1 mice with DI or saline. Our results showed that DI ameliorated the cognitive deficits of APP/PS1 mice. Further, DI significantly decreased brain Aß deposition and Aß levels, inhibited cell apoptosis, decreased hippocampal and cortical neuronal damage. We also found that DI promoted the expression of the Nrf2/HO-1 signaling pathway, while inhibited cognitive impairment, cell apoptosis, and the proinflammatory cytokine levels in the brains of APP/PS1 mice. Our results indicated that DI attenuated memory impairment and neuroinflammation via the Nrf2 signaling pathway in APP/PS1 mice, suggesting that DI might be recognized as a promising candidate for the treatment of AD.

Life-threatening complications after microvascular decompression procedure: Lessons from a consecutive series of 596 patients.

The microvascular decompression procedure (MVD) is widely utilized on patients with neurovascular compression syndromes, such as trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia, which have failed medical therapy. However, surgical complications are an ongoing problem. We retrospectively reviewed a total of 596 patients undergoing MVD in the Affiliated Hospital of Qingdao University from January 2008 to December 2018. Furthermore, we discussed the cases with life-threatening complications to determine the potential causes, aiming to achieve the goal of safer microvascular decompression. There were seven cases with life-threatening complications. Of those complications, one was cerebellar infarction with acute hydrocephalus, one was infarction of the cerebellum and the brain stem with acute hydrocephalus and serious intracranial infection, two were cerebellar haematoma, one was multiple haemorrhage with acute hydrocephalus, one was supratentorial subdural haematoma, and one was cerebellar swelling with acute hydrocephalus. After therapy, one patient died, one was in a persistent vegetative state, and five were discharged from the hospital upon recovery. In brief, MVD is a safe operation, and life-threatening complications accompanying MVD are rare, but require attention. The causes of some life-threatening complications are still not completely clear. Surgeons should continuously improve surgical techniques and perioperative care to reduce potential risks.

Identification of 2 Potential Core Genes for Influence of Gut Probiotics on Formation of Intracranial Aneurysms by Bioinformatics Analysis.

BACKGROUND Rupture of intracranial aneurysms (IA) is associated with high rates of mortality around the world. Use of intestinal probiotics can regulate the pathophysiology of aneurysms, but the details of the mechanism involved have been unclear. MATERIAL AND METHODS The GEO2R analysis website was used to detect the DEGs between IAs, AAAs, samples after supplementation with probiotics, and normal samples. The online tool DAVID provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs was analyzed based on the STRING database, followed by analysis using Cytoscape software. RESULTS We found 170 intersecting DEGs (contained in GSE75240 and more than 2 of the 4 aneurysms datasets), 5 intersecting DEGs (contained in all datasets) and 1 intersecting DEG (contained in GSE75240 and all IAs datasets). GO analysis results suggested that the DEGs primarily participate in signal transduction, cell adhesion, immune response, response to drug, extracellular matrix organization, cell-cell signaling, and inflammatory response in the BP terms, and the KEGG pathways are mainly enriched in focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, amoebiasis, chemokine signaling pathway, proteoglycans, and PI3K-Akt signaling pathway in cancer pathways. Through PPI network analysis, we confirmed 2 candidates for further study: CAV1 and MYH11. These downregulated DEGs are associated with the formation of aneurysms, and the change of these DEGs is the opposite in probiotics-treated animals. CONCLUSIONS Our study suggests that MYH11 and CAV1 are potential target genes for prevention of aneurysms. Further experiments are needed to verify these findings.

Intracranial Mirror Aneurysm: Epidemiology, Rupture Risk, New Imaging, Controversies, and Treatment Strategies.

There are some controversies about the surgical treatment strategy of mirror aneurysms. Whether to choose 1-stage or 2-stage surgery, bilateral or unilateral craniotomy, or surgical or interventional treatment are the main points in dispute. In this review, the different surgery strategies faced by patients are discussed. Different surgical methods are adopted based on the patient's individual state and the location and size of the aneurysm. A new imaging method is introduced using 3D Slicer, which clearly recognizes the relationship among aneurysm, brain tissue, skull, and nerve. The 3D Slicer can help surgeons undertake adequate preoperative preparation. In addition, we also introduce some ruptured factors (e.g., age, gender, hypertension, morphologic, and hemodynamic) concerning mirror aneurysm. Systematic discussion of the controversies and methods in surgical treatment of mirror aneurysms may provide new perspectives in future research for the prevention and treatment of mirror aneurysms.