Preoperative prognostic nutrition index can independently predict the 6-month prognosis of elderly patients undergoing neurosurgical clipping for aneurysmal subarachnoid hemorrhage.

The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) is increasing annually. The prognostic nutritional index (PNI) is used as a novel and valuable prognostic marker for various neoplastic diseases and other critical illnesses. This study aimed to identify the short-term prognostic value of preoperative PNI in elderly patients who underwent neurosurgical clipping for aSAH. This retrospective study included elderly patients with aSAH who underwent neurosurgical clipping from January 2018 to December 2020. Clinical variables and 6-month outcomes were collected and compared. Epidemiological data and effect factors of prognosis were evaluated. Multivariate logistic regression and receiver operating characteristics (ROC) curve analyses were used to evaluate the predictive value of preoperative PNI. Multiple logistic regression was performed to establish a nomogram. A total of 124 elderly patients were enrolled. Multivariate logistic regression analysis showed that preoperative PNI (odds ratio (OR), 0.779; 95% confidence interval (CI), 0.689-0.881; P < 0.001), Hunt-Hess grade (OR, 3.291; 95%CI, 1.816-5.966; P < 0.001), and hydrocephalus (OR, 9.423; 95%CI, 2.696-32.935; P < 0.001) were significant predictors. The area under the ROC curve of PNI was 0.829 (95% CI, 0.755-0.903; P < 0.001) with a sensitivity and specificity of 68.4% and 83.3%, respectively, and the cutoff value was 46.36. Patients with preoperative PNI of < 46.36 had a significantly unfavorable 6-months prognosis (F = 40.768, P < 0.001). Preoperative PNI is independently correlated with the 6-month prognosis in elderly patients who undergo neurosurgical clipping for aSAH.

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.

Glycine confers neuroprotection through PTEN/AKT signal pathway in experimental intracerebral hemorrhage.

Glycine has been shown to protect against ischemic stroke through various mechanisms. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) which antagonize Akt-dependent cell survival has been linked to neuronal damage. However, whether glycine has a neuroprotective property in intracerebral hemorrhage (ICH) was unknown. This study aimed to determine the protective effect of glycine in rats ICH. Adult male Sprague-Dawley (SD) rats were subjected to left striatum infusion of autologous blood. ICH animals received glycine (0.2-3 mg/kg, icv) at 1 h after ICH with or without pre-injection of Akt Inhibitor IV (100 µM, 2 µl, icv) 0.5 h prior to glycine treatment. Our results showed that in the perihematomal area PTEN was up-regulated in the early stage after ICH. However, glycine treatment decreased PTEN protein level and increased the phosphorylation level of AKT (p-AKT) in the perihematomal area. With the administration of glycine, neuronal death was significantly reduced and Evans blue leakage was alleviated as well as the brain edema after ICH. Moreover, hematoma volume was decreased and neurobehavioral outcome was improved. Nevertheless, Akt Inhibitor IV abolished the neuroprotective effects of glycine after ICH. Together, our findings demonstrate, for the first time, the protective role of glycine on ICH rats, and suggest that the neuroprotective effect of glycine was mediated through PTEN/Akt signal pathway.

Effects of estrogen receptor GPR30 agonist G1 on neuronal apoptosis and microglia polarization in traumatic brain injury rats.

PURPOSE: To investigate the effects of estrogen G protein-coupled receptor 30 (GPR30) agonist G1 on hippocampal neuronal apoptosis and microglial polarization in rat traumatic brain injury (TBI). METHODS: Male SD rats were randomly divided into sham group, TBI + vehicle group, TBI + G1 group. Experimental moderate TBI was induced using Feeney's weigh-drop method. G1 (100µg/kg) or vehicle was intravenously injected from femoral vein at 30 min post-injury. Rats were sacrificed at 24 h after injury for detection of neuronal apoptosis and microglia polarization. Neuronal apoptosis was assayed by immunofluorescent staining of active caspase-3. M1 type microglia markers (iNOS and IL-1ß) and M2 type markers (Arg1 and IL-4) were examined by immunoblotting or ELISA. Total protein level of Akt and phosphorylated Akt were assayed by immunoblotting. RESULTS: G1 significantly reduced active caspase-3 positive neurons in hippocampus. Meanwhile G1 increased the ratio of Arg1/iNOS. IL-1ß production was decreased but IL-4 was increased after G1 treatment. G1 treatment also increased the active form of Akt. CONCLUSIONS: GPR30 agonist G1 inhibited neuronal apoptosis and favored microglia polarization to M2 type.

Primary endodermal sinus tumor in the posterior cranial fossa: clinical analysis of 7 cases.

OBJECTIVE: To clarify the clinical features, therapeutic method and outcomes of the primary endodermal sinus tumors (ESTs) in the posterior cranial fossa. METHODS: The English literatures on EST in the posterior cranial fossa were retrieved from PubMed and reviewed. And a 4-year-old boy diagnosed with EST in our hospital was reported. The clinical manifestations, therapy, pathologic features, and prognosis of these cases were analyzed. RESULTS: Only seven cases of the ESTs in the posterior cranial fossa were enrolled in this review, including six cases searched from the PubMed and one case from our hospital. Six patients were boy and one patient's gender was not available from the report. Ages ranged from 1 to 5 years (mean 3.14 years). The mean tumor size in our cohort was 4.4 cm. Six cases came from East Asia. Schiller-Duval bodies were found in all seven neoplasms. All tumors were positive for alpha-fetoprotein. The alpha-fetoprotein level in serum was increased to a very high level before therapy and depressed quickly after the effective chemotherapy. The mean follow-up time was 24.4 months (range 5-52 months). Six tumors were totally removed, and four of them recurred. Three cases died including one whose tumor was partially removed. CONCLUSIONS: The serum alpha-fetoprotein level is well correlated with the severity of the tumor. A combination of operation and chemotherapy might be the effective management for EST in the posterior cranial fossa. The prognosis of extragonadal intracranial EST is poor.

Predictors of Oculomotor Nerve Palsy with Posterior Communicating Aneurysm Clipping in a Surgically Treated Series of 585 Patients: A Single-Center Study.

BACKGROUND: Oculomotor nerve palsy (OMNP) is a known risk in surgical management of intracranial aneurysms. The aim of this study was to determine the risk factors for surgery-induced OMNP. METHODS: This retrospective study examined 585 patients with posterior communicating artery aneurysms treated surgically between January 2000 and July 2019. The patients were categorized into 2 groups according to whether they experienced OMNP. Multiple factors, including sex, age, history of subarachnoid hemorrhage, Hunt and Hess grade, Fisher grade, preoperative time, sizes, sides, number, orientation, intraoperative rupture, and morphology, were analyzed to identify factors associated with surgery-induced OMNP. RESULTS: The overall OMNP rate was 4.4%. In univariate analysis, large size (P < 0.001), posterior infratentorial projection (P = 0.003), number of subarachnoid hemorrhages (P = 0.005), and late preoperative time (P < 0.001) were associated with increased risk of OMNP. Overall, multivariate logistic regression analysis showed that size (10.1-25 mm: odds ratio [OR] 30.083, P = 0.001, 95% confidence interval [CI], 3.703-244.419; >25 mm: OR 62.179, P = 0.012, 95% CI, 2.402-1609.418), intraoperative rupture (OR 3.018, P = 0.035, 95% CI, 1.083-8.412), and preoperative time (>14 days: OR 10.985, P < 0.001, 95% CI, 3.840-31.428) were independent risk factors of surgery-induced OMNP. CONCLUSIONS: This study showed that size, intraoperative rupture, and preoperative time were independent predictors of surgery-induced OMNP. Use of advanced technologies during the operation can assist in avoiding this complication.

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.

Down-regulation of TGF-ß RII expression is correlated with tumor growth and invasion in non-functioning pituitary adenomas.

The two types of TGF-ß receptors play a crucial role in TGF-ß signaling. It has been reported that TGF-ß signaling activity may be associated with the development and invasion of NFPAs. However, the role of TGF-ß receptor signaling in NFPAs has not been fully explored. In this study, the expression of TGF-ß RI and TGF-ß RII in normal anterior pituitaries, invasive NFPAs and non-invasive NFPAs was analyzed by qRT-PCR, western blot, and immunohistochemistry. We found that TGF-ß RII protein and mRNA levels gradually decreased from normal anterior pituitaries, noninvasive NFPAs to invasive NFPAs. There was no significant difference in the expression of TGF-ß RI mRNA and protein level between normal anterior pituitaries and NFPAs. PCNA mRNA level was significantly higher in the invasive NFPAs than noninvasive NFPAs and PCNA mRNA had a negative correlation with TGF-ß RII mRNA. We may draw the conclusion that low expression of TGF-ß RII may contribute to the development and invasion of NFPAs and TGF-ß RII promises to be a useful biomarker for the diagnosis of invasive NFPAs.

Upregulation of microRNA­24 causes vasospasm following subarachnoid hemorrhage by suppressing the expression of endothelial nitric oxide synthase.

MicroRNA (miR)­24 has been reported to associate with various diseases by acting on different signaling pathways. The present study aimed to elucidate the association between miR­24 expression levels and vasospasm following subarachnoid hemorrhage (SAH), and its underlying mechanism. An miR online database was searched, identifying endothelial nitric oxide synthase (NOS3) as a potential target gene of miR­24. A luciferase reporter assay performed to investigate the regulatory association between miR­24 and NOS3 revealed that miR­24 bound to the NOS3 3' untranslated region and inhibited NOS3 expression. Reverse transcription­quantitative polymerase chain reaction and western blot analysis were performed to investigate the miR­24 and NOS3 expression levels in samples from patients with SAH, and demonstrated a negative correlation between the two. In addition, miR­24 expression levels were increased in SAH patients with vasospasm compared with those without, whereas the opposite results were observed for NOS3. Vascular smooth muscle cells (VSMCs) transfected with an miR­24 inhibitor exhibited increased expression levels of NOS3, whereas those transfected with an miR­24 mimic or NOS3 small interfering RNA exhibited reduced expression levels of NOS3, compared with the control. These results indicated a negative regulatory association between miR­24 and NOS3. Downregulation of NOS3 may induce vasospasm following SAH, which may be due to the upregualtion of miR­24 in VSMCs.

DJ-1 Suppresses Cytoplasmic TDP-43 Aggregation in Oxidative Stress-Induced Cell Injury.

DJ-1 (also called PARK7) is a multifunctional redox-sensitive protein that is protective against oxidative stress-induced cell death. TAR DNA-binding protein 43 (TDP-43) is a major protein component of pathological inclusions in amyotrophic lateral sclerosis and frontotemporal dementia. Reducing aberrant aggregation of TDP-43 is a potential approach to prevent cell death. To investigate whether DJ-1 might inhibit TDP-43 aggregation to exert a protective effect in oxidative stress-induced injury, we tested the protein level and subcellular localization of TDP-43 and DJ-1 in SH-SY5Y cells transfected with wild-type DJ-1, DJ-1 mutant (L166P) cDNA, or DJ-1 siRNA. We show that oxidative stress induced by paraquat leads to the formation of cytosolic TDP-43 aggregation in SH-SY5Y cells. DJ-1 overexpression decreases paraquat-induced cytoplasmic accumulation of TDP-43 in SH-SY5Y cells and protects against paraquat-induced cell death. Transfection of DJ-1 L166P mutant or DJ-1 siRNA leads to increased cytosolic aggregation of TDP-43 in paraquat-treated SH-SY5Y cells and promotes cell death. These data suggest that DJ-1 may protect against oxidative stress-induced cell death through the suppression of cytoplasmic TDP-43 aggregation.

Effect of combined VEGF165/ SDF-1 gene therapy on vascular remodeling and blood perfusion in cerebral ischemia.

OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral infarction.

A young and booming approach: the extreme lateral supracerebellar infratentorial approach.

Surgical accesses to lesions of the posterolateral pontomesencephalic junction (PMJ) region and the posterolateral tentorial gap remain a challenge in the field of neurosurgery. Since the first report of application of the extreme lateral supracerebellar infratentorial (ELSI) approach in resecting the PMJ lesions in 2000, a few articles concerning the ELSI approach have been published. The present review mainly provided an intimate introduction of the ELSI approach, and evaluated it in facets of patient position, skin incision, craniectomy, draining veins, retraction against the cerebellum, exposure limits, patient healing, as well as advantages and limitations compared with other approaches. The ELSI approach is proposed to be a very young and promising approach to access the lesions of posterolateral PMJ region and the posterolateral tentorial gap. Besides, it has several advantages such as having a shorter surgical pathway, causing less surgical complications, labor-saving, etc. Still, more studies are needed to improve this approach.