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Pain is a major complication of cancer and significantly affects the quality of life. Cerebrospinal fluid-contacting nucleus (CSF-CN) has been reported to be involved in the development of neuropathic pain and inflammatory pain. However, whether CSF-CN contributes to cancer-induced bone pain (CIBP) remains unknown. In this study, we aimed to illustrate the role of CSF-CN in the pathogenesis of CIBP and identify its potential mechanism via the MKP-1-mediated MAPK pathway. The Walker 256 cancer cells were injected into the tibia cavity of female Sprague-Dawley rats to induce CIBP models. Intracerebroventricular injection of cholera toxin subunit B- saporin (CB-SAP) was performed to "knockout" the CSF-CN. Morphine and LV-MKP-1 were applied. Mechanical and thermal hyperalgesia behaviors, double immunofluorescence staining and Western blot were conducted after CIBP induction. The results revealed that CIBP significantly reduced the mechanical withdrawal threshold and the thermal threshold. Double immunofluorescence staining revealed that c-Fos-positive neurons in CSF-CN were significantly higher in the CIBP group than that in the sham group. Targeted ablation of CSF-CN dramatically aggravated pain sensitivity. Moreover, MKP-1 was down-regulated in the CSF-CN after CIBP induction. Pharmacological intervention with morphine significantly ameliorated the mechanical and thermal hyperalgesia through reversing the down-expression of MKP-1 in the CSF-CN on day 14 after CIBP induction. Mechanically, overexpression of MKP-1 by LV-MKP-1 injection significantly relieved CIBP via inhibiting the expression of phosphorylated p38, which subsequently decreased the protein levels of Bax, cleaved caspase-3 and Iba-1, and reduced the mRNA levels of IL-1β, TNF-α and IL-6 in CSF-CN. In conclusion, CSF-CN contributed to CIBP via regulating the MKP-1-mediated p38-MAPK pathway. Future therapy targeting the expression of MKP-1 in the CSF-CN may be a promising new choice.

Background Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. Methods GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. Results The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. Conclusion Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.

Glioblastoma (GBM) is a highly heterogeneous disease with poor clinical outcome.To comprehensively dissect molecular landscape of GBM and heterogeneous distribution and potential role of Enhancer of zeste homolog 2 (EZH2) in tumor microenvironment (TME).Single-cell RNA sequencing (scRNA-seq) analysis was performed in GBM samples from 8 patients. Deconvolution analysis, immunofluorescence (IF) microscopy, reverse-transcription quantitative polymerase chain reaction (RT-qPCR), colony formation experiments, and Cell Counting Kit-8 (CCK-8) assays were performed to confirmed the potential role of EZH2 in TME cells.Malignant cells exhibited remarkable heterogeneity in abnormal metabolic patterns. A mesenchymal-2-like (MES2-like) GBM subcluster with glial-immune dual feature was firstly discovered, which were associated with highly activated hallmark pathways, immune evasion associated transcription factor (IRF8), and poor survival. The oncogene, EZH2, was heterogeneously expressed in malignant cells and immune cells consistent with proliferative genes, cell-cycle transcription factors, and similar activated hallmark pathways. In a tumor-associated macrophages (TAMs) subset (macrophage.3), EZH2 was highly expressed with similar changes of transcriptomic dynamics with cell-cycle genes and macrophages M2-phetotype genes. In addition, the subset tightly interacted with malignant cells. Deconvolution analysis showed increased abundance of the subset in GBM compared to low-grade glioma (LGG) and significant association with worse prognosis. Functional verification experiments confirmed the pro-tumor role of TAMs with EZH2 overexpression in GBM.Our study illustrated a MES2-like GBM subcluster characterized by glial-immune dual feature and highlighted the pro-tumor role of a TAMs subset characterized by EZH2 overexpression.

Objective: We assessed the correlation between lactate dehydrogenase(LDH) to phosphate ratio and the prognosis of microsurgically clipping for ruptured intracranial aneurysm (rIA) in this study, to test the hypothesis that serum LDH to phosphate ratio could be a predictor for the outcome of microsurgically clipping for rIA. Methods: The rIA patients between 2012 and 2018 were retrospectively collected. Age, sex, Hunt-Hess(H-H) grade, Fisher grade, smoking, drink, medical history, aneurysm location, hydrocephalus, laboratory data including serum LDH, phosphate and LDH to phosphate ratio, related complication and the outcomes in 3 months were recorded. Results: A total of 1608 rIA patients in our institution were collected, and 856 patients treated by microsurgical clipping were enrolled. A significantly higher LDH- phosphate ratio on admission was observed in patients with poor outcome at 3 months (median±SD, 200.175±107.290 for mRS 0–2 vs 323.826±219.075 for mRS score 3–6; P Conclusions: LDH to phosphate ratio was a potential biomarker and could predict the unfavorable outcome of microsurgically clipping for rIA in 3 months. However, the detailed mechanism remain unclear and the conclusion needs be further confirmed by large-scale randomized clinical trials.

Background and Purpose— Hypoxic-ischemic brain damage is a well-recognized physiopathologic mechanism after aneurysmal subarachnoid hemorrhage (aSAH). The Ngb (neuroglobin) is a hemoprotein predominantly expressed in the brain with a high affinity for oxygen. Relationship between serum Ngb level and brain metabolism in aSAH patients has not been investigated previously. Methods— Thirty-six consecutive severe aSAH patients (Glasgow Coma Scale score ≤8 on admission) with multimodal neuromonitoring and 36 matched healthy subjects were included. Serum Ngb level was analyzed in combination with other time-matched cerebral microdialysis parameters, brain tissue oxygen tension, and 12-month neurological outcomes. Results— Serum Ngb level was correlated positively with cerebral microdialysis parameters and brain tissue oxygen tension ( P 3) 12 months after aSAH was associated with higher Ngb level but independent of age, sex, and disease severity ( P P Conclusions— Ngb may be a potential biomarker for reflecting brain tissue oxygen tension, brain metabolism, and functional outcome in severe aSAH patients and merits further study in the context of aSAH.

Background Chondrosarcoma is a malignant tumor that originates from mesenchymal cells that have differentiated into chondrocytes, often growing laterally, rarely seen in the cranium, and seldom seen in the saddle area. We believe that only a few cases have been reported in the literature. We report a case of pituitary fossa chondrosarcoma, which was completely resected by an extended endoscopic endonasal approach, and a literature review. Case Description A 20-year-old man was admitted to hospital with bilateral temporal headache and blurred vision, without any history of sexual dysfunction or diabetes insipidus. Endocrine function was normal. Computed tomography of the head showed calcified sellar lesions and sellar bone destruction, which were closely associated with the right cavernous sinus. Magnetic resonance imaging showed saddle area space-occupying lesions, with low signal on the T1-weighted image and high signal on the T2-weighted image, uneven enhancement by enhanced scanning, and unclear pituitary display. The tumor was completely resected by an extended endoscopic endonasal approach and confirmed by magnetic resonance imaging. Postoperative pathology revealed conventional chondrosarcoma (World Health Organization grade II). Postsurgical visual acuity also improved. The patient did not receive radiotherapy or chemotherapy. No recurrence was found at 10-month follow-up. Conclusions Sellar region chondrosarcoma is rare. For space-occupying lesions in this area, chondrosarcoma should be considered and not necessarily pituitary adenoma, craniopharyngioma, meningioma, and chordoma. The extended endoscopic endonasal approach represents a good treatment option for sellar area chondrosarcoma.

The aim of the study is to investigate the value of serum iron and hemoglobin levels for predicting acute seizures following aneurysmal subarachnoid hemorrhage (aSAH). Clinical and laboratorial data from patients with ruptured intracranial aneurysms were collected in the retrospective study. Age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt–Hess grade, Fisher grade, aneurysm location, hemoglobin, serum potassium, sodium, calcium, phosphorus, and iron were collected. Acute seizures were determined as seizures within 1 week following aSAH. Propensity score matching (PSM) analyses were performed to correct imbalances in patient characteristics between seizure and non-seizure groups. A total of 760 patients were included. Incidence of acute seizures following aSAH was 6.4%. In the univariate analysis, significant differences were detected in age, admission Hunt–Hess grade, Fisher grade, hemoglobin, serum sodium, and serum iron between seizure and non-seizure groups. In multivariate logistic regression model, lower serum iron was considered as a risk factor for acute seizures (OR 0.182, 95% CI 0.084–0.393, p = 0.000), as well as lower hemoglobin (OR 0.977, 95% CI 0.962–0.993, p = 0.004) and higher serum sodium (OR 1.072, 95% CI 1.003–1.145, p = 0.039). After PSM, there were no significant differences in age, admission Hunt–Hess grade, Fisher grade, and serum sodium between seizure and non-seizure groups. The matched seizure group had lower serum iron and hemoglobin levels compared with the matched non-seizure group (p

Background There is associating with incidence of unfavorable outcomes compared to microsurgical clippings. We are in order to investigate the outcomes of microsurgical clipping for intracranial aneurysms and determine the ideal clipping methods for different aneurysm subtypes. Method Retrospectively analyzed the clinical characteristics and follow-up data (completely recorded) of 123 patients with 128 aneurysms were treated. 20 cases were treated as control group from October 2013 to December 2013. Since January 2014, aneurysms were classified base on the 20 cases of aneurysm imaging data. 103 patients were treated as experimental group, the classification of aneurysms previously proposed was used to estimate the way of surgery, and the guiding value of the genotype was verified according to the intraoperative findings. The proposed aneurysm classification is based on the virtual surface of the aneurysm and the parent artery, the aneurysm neck was classified as follows: subtype I, the curved surface of the neck is a single curved surface; subtype II, the neck is hyperboloid; subtype III, neck is a three-curved surface. Aneurysms were divided into further subtypes according to the ratio of the width of the aneurysm neck surface and the length of the artery circumference: subtype A, the ratio of the aneurysm neck surface to the parent artery was not more than 0.5; subtype B, more than 0.5. There are some clamping methods include simple, sliding, interlocking and hybrid. Results In the control group, patients did not undergo a suitable clipping scheme without classification of aneurysm neck (unclassed clipping). While causing the occurrence of occlusion adverse events, including neck residual, Tumor artery stenosis, electrophysiological changes, the lack of blood supply and so on. The experimental[page1image12073600]group was analyzed by using a predetermined clipping scheme (classed clipping), and the use of aneurysms clamps was approximately the same as expected. Compared the preoperative assessment with the actual situation, the consistency of the control group was 50% and the experimental group was 96%. Adverse events of classed clipping is 2%, another is 60%. There is a significant difference between the two groups (P

Additional file 2: Table S2. The oligo sequences for transfection in this study.

Additional file 1: Table S1. The primer sequences for qRT-PCR in this study.

Background Temozolomide (TMZ) resistance limits its application in glioma. Exosome can carry circular RNAs (circRNAs) to regulate drug resistance via sponging microRNAs (miRNAs). miRNAs can control mRNA expression by regulate the interaction with 3’UTR and methylation. Nanog homeobox (NANOG) is an important biomarker for TMZ resistance. Hitherto, it is unknown about the role of exosomal hsa_circ_0072083 (circ_0072083) in TMZ resistance in glioma, and whether it is associated with NANOG via regulating miRNA sponge and methylation. Methods TMZ-resistant (n = 36) and sensitive (n = 33) patients were recruited. The sensitive cells and constructed resistant cells were cultured and exposed to TMZ. circ_0072083, miR-1252-5p, AlkB homolog H5 (ALKBH5) and NANOG levels were examined via quantitative reverse transcription polymerase chain reaction and western blot. The half maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, migration and invasion were analyzed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing and transwell assays. The in vivo function was assessed using xenograft model. The N6-methyladenosine (m6A) level was analyzed via methylated RNA immunoprecipitation (MeRIP). Target relationship was investigated via dual-luciferase reporter assay and RNA immunoprecipitation. Warburg effect was investigated via lactate production, glucose uptake and key enzymes expression. Exosome was isolated and confirmed via transmission electron microscopy and specific protein expression. Results circ_0072083 expression was increased in TMZ-resistant glioma tissues and cells. circ_0072083 knockdown restrained the resistance of resistant cells via decreasing IC50 of TMZ, proliferation, migration, invasion and xenograft tumor growth and increasing apoptosis. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. circ_0072083 could regulate NANOG and ALKBH5 via targeting miR-1252-5p to control TMZ resistance. Warburg effect promoted the release of exosomal circ_0072083 in resistant cells. Exosomal circ_0072083 from resistant cells increased the resistance of sensitive cells to TMZ in vitro and xenograft model. Exosomal circ_0072083 level was enhanced in resistant patients, and it had a diagnostic value and indicated a lower overall survival in glioma. Conclusion Exosomal circ_0072083 promoted TMZ resistance via increasing NANOG via regulating miR-1252-5p-mediated degradation and demethylation in glioma.

Background: Studies investigating the change in distance between the bilateral internal carotid arteries (ICAs) in acromegalic patients have provided ambiguous results. The influencing factors of these changes have not been well-identified. Objective: To further investigate the change in distance between bilateral ICAs in acromegaly patients and identify the influencing factors of the change. Method: Patients diagnosed as acromegaly from Jan 2016 to Sep 2019 in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University, were included in this study. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) data were obtained for all patients for three-dimensional reconstruction of the ICAs. Distance between bilateral ICAs was measured and recorded for assessment. Result: 172 patients including 86 cases with acromegaly in the study group and 86 cases with non-functional pituitary adenoma in the control group were enrolled in this study. The difference of adenoma sizes between two groups was not statistically significant. Patients in acromegaly group had significantly larger maximum distances between bilateral siphon carotid ectasias (25.5 ± 4.1 vs. 23.4 ± 3.5 mm, P = 0.001) and between bilateral lacerum segments (26.2 ± 3.2 vs. 24.1 ± 4.3 mm, P < 0.001) compared with those of patients with non-functional pituitary adenomas. Multivariate analysis showed that the increased bilateral ICAs distance was associated with disease duration (odds ratio = 1.01, 95% confidence interval = 1.01–1.02, P = 0.005) and refractory pituitary adenoma (odds ratio = 9.8, 95% confidence interval = 1.1–88.7, P = 0.043) but not with level of growth hormone (GH), insulin-like growth factor-1 (IGF-1) and adenoma size in acromegaly. Conclusion: Our study showed significant change in distance between the bilateral ICAs in acromegalic patients, comparing to patients with non-functional pituitary adenomas. The increased intercarotid artery distance is associated with disease duration but not with preoperative level of GH and IGF-1. Refractory pituitary adenoma and longer disease duration are the both risk factors of the increased ICAs distance in patient with acromegly.

Background: To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically-controlled surgery with open hemi-laminectomy technique.Methods: In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically-controlled surgery with open hemi-laminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis.Results: All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short term follow-up data showed that there was no tumor recurrence or spinal deformity. Conclusion: The endoscopically-controlled surgery with open hemi-laminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.

Background Inflammation has been believed to be related to the development of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH). A potential biomarker for vascular inflammation that is well recognized is the lipoprotein-associated phospholipase A2 (Lp-PLA2). However, whether Lp-PLA2 can predict the occurrence of symptomatic cerebral vasospasm (SCV) in aSAH patients is still unknown. Thus, this study aimed to assess the value of Lp-PLA2 for predicting SCV in patients with aSAH. Methods Between March 2017 and April 2018, we evaluated 128 consecutive aSAH patients who were admitted in the First Affiliated Hospital of Fujian Medical University. Their Lp-PLA2 level was obtained within 24 h of the initial bleeding. Factors might be related to SCV were analyzed. Results Compared to patients without SCV, those with SCV (9.4%, 12/128) had significantly higher Lp-PLA2 level. Multivariate logistic analysis revealed that worse modified Fisher grade (OR = 10.08, 95% CI = 2.04–49.86, P = 0.005) and higher Lp-PLA2 level (OR = 6.66, 95% CI = 1.33–3.30, P = 0.021) were significantly associated with SCV, even after adjustment for confounders. Based on the best threshold, Lp-PLA2 had a sensitivity of 83.3% and a specificity of 51.7% for predicting SCV, as shown by the receiver operating characteristic curve analysis. In the poor World Federation of Neurosurgical Societies grade patient sub-group, patients with Lp-PLA2 > 200 μg/L had significantly higher SCV rate than that of patients having Lp-PLA2 ≤ 200 μg/L. Conclusion The admission Lp-PLA2 level might be a helpful predictor for SCV in aSAH.

Background The neuroglobin (Ngb) is well recognized as a potential biomarker for the hypoxic‐ischemic brain injury. However, connection between Ngb and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is still unclear. Objective To investigate the relationship between early stage Ngb level of aSAH patient and the occurrence of DCI. Methods We evaluated 126 aSAH patients who were enrolled into a prospective observational cohort study. Serum Ngb level on days 1, 2, 3, 5, and 7 after aSAH were determined using a commercial enzyme‐linked immunosorbent assay kit. The relationship between Ngb level and DCI was analyzed. Results Forty‐six (36.5%) aSAH patients experienced DCI. Patients with DCI had significantly higher Ngb levels than those without (p 8.4 ng/ml has a significantly worse DCI survival rate than those having day 3 Ngb level, Although qualitative or semiquantitative clinical grades (such as WFNS grade and modified Fisher grade) are well known to be associated with DCI following aSAH, identification of an easily measurable and more objective biomarker for predicting DCI might be helpful for early prediction and risk mitigation. In the current study, we found that the early stage neuroglobin level was a significant predictor of DCI in aSAH patients. Furthermore, combined use of WFNS grade and Ngb level might be able to better identify aSAH patients with high risk of DCI.

OBJECTIVE: To evaluate the feasibility of applying intracranial lead reconstruction in deep brain stimulation (DBS) therapy for Parkinsonism. METHODS: We retrospectively collected the clinical data from 27 patients with Parkinson's disease (PD), who received bilateral subthalamic nucleus (STN) DBS therapy between January, 2016 and December, 2017. According to the position of the selected optimal stimulating contact of the implanted leads, the patients were divided into group A with the stimulating contacts of the bilateral leads in the STN, group B with unilateral stimulating contacts in the STN, and group C with bilateral stimulating contacts outside the STN. All the patients were assessed for improvement using Hoehn-Yahr stage, the third part of United Parkinson's Disease Rating Scale (UPDRS Ⅲ), Schwab and England Activities of Daily Living (SE-ADL), and L-dopa equivalent daily dose (LEDD). The consistency between the optimal stimulating contact selected by lead reconstruction and that by standard postoperative programming procedure was also evaluated. RESULTS: The patients in all the 3 groups showed postoperative improvements in Hoehn-Yahr stage, UPDRS Ⅲ score, SE-ADL score, and LEDD in the medication-off state. But at 12 months of the follow-up, such improvements were maintained only in the patients of group A. The optimal stimulating contacts selected by lead reconstruction and standard postoperative programming procedure had a matching rate of up to 77.78% (42/54), and the coordinates of the optimal contacts selected by the two methods showed no significant difference. CONCLUSION: Intracranial lead reconstruction facilitates the study of the association between the implant site of the leads and the clinical outcome of DBS therapy for PD and allows the precise selection of the optimal contact of the implanted leads in postoperative programming of DBS.

BACKGROUND Controversies exist in imaging modalities for predicting adenoma consistency. In this study, we proposed a method of predicting consistency by magnetic resonance T2-sequence imaging based on adenoma to cerebellar peduncle signal (TCTI) ratio. MATERIAL AND METHODS Between January 2013 and May 2017, 191 consecutive patients with pituitary adenoma diagnosed at our institution were retrospectively studied. The consistency grade for each lesion was assigned. And the TCTI ratio based on preoperative and postoperative T2-weighted imaging was calculated. RESULTS The median TCTI ratio was 1.55, 1.28, and 1.25 for soft, fibrous, and hard adenomas, respectively. The differences were significant for all groups (p

It is not fully established whether leukocyte can predict the poor outcome for ruptured cerebral aneurysms (CA) or not. Here, we retrospectively analyzed the clinical data of 428 patients with ruptured CA between 2010 and 2015. Patients’ demographic data, including gender, age, history of smoking, alcohol, hypertension, diabetes and hypercholesterolemia, Hunt-Hess and Fisher grade, occurrence of hydrocephalus, aneurysm location, time to surgery, delayed ischemic neurological deficit (DIND) and peak leukocyte of blood test from day 1 to 3 after aneurysmal rupture were recorded and analyzed. In the multivariable analysis model, gender, Fisher grade, time to surgery and hydrocephalus were not relevant to poor outcome. However, Hunt-Hess grade, DIND and preoperative leukocyte count (>13.84 × 109/L) were significantly associated with adverse outcome. The respective increased risks were 5.2- (OR 5.24, 95% CI 1.67–16.50, p = 0.005), 6.2-(OR 6.24, 95% CI 3.55–10.99, p 13.84 × 109/L) were independent risk factors for poor outcome of ruptured CA at 3 months. Higher leukocyte count is a convenient and useful marker to predict 3-month poor outcome for ruptured CA.

Background The prevalence rates of freezing of gait (FOG) in Parkinson’s disease (PD) vary widely, ranging from 14.0 to 55.1%. Our aim is to calculate the overall prevalence of FOG in all PD patients with different disease durations and severities. Methods Using Medline/PubMed/Embase, we carried out a systematic literature search for studies reporting the PD and clinically relevant FOG. Results After primary screening, a total of 35 studies were identified and further analyzed for inclusion into the analysis, and 29 studies fulfilled the quality criteria and included in this meta-analysis. The overall prevalence of FOG in PD was 39.9% (95% CI 35.3-44.5%). The FOG identified by the freezing of gait questionnaire item 3 may be more prevalent (43.8%, 95% CI 38.5-49.1%) than the FOG identified by the Unified Parkinson’s Disease Rating Scale item 14 (36.0%, 95% CI 29.0-43.1%). Disease duration and severity are both the clinical features associated with the FOG. The highest FOG prevalence rate in PD patients was seen in patients with disease durations ≥ 10 years, at 70.8%, followed that of PD patients with disease durations ≥ 5 years (53.3%), and PD patients with disease durations < 5 years (22.4%). FOG presented in 28.4% of PD patients with Hoehn and Yahr staging (H&Y) score ≤ 2.5, and in 68.4% of PD patients with H&Y score ≥ 2.5. Conclusion This meta-analysis confirms that the prevalence of FOG in PD is considerable, and highlights the need for accurate identification of FOG in PD.

We aimed to demonstrate the effects of microRNA (miR)-101 on neuropathic pain and explore the underlying mechanisms. Rat spinal microglia cells were isolated and inflammatory condition was stimulated by 24-h incubation with lipopolysaccharide (LPS). Rats were divided into 4 groups: sham, chronic constriction injury (CCI), CCI + miR-negative control (miR-NC) and CCI + miR-101 mimics. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) tests were conducted. The mRNA levels of key genes were determined by quantitative real-time polymerase chain reaction. Mammalian target of rapamycin (mTOR) protein level was detected by Western blot. Concentrations of interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were examined by ELISA. MiR-101 was downregulated and mTOR was upregulated in lumbar spinal dorsal horns from CCI rats. Targetscan and luciferase reporter assay confirmed that mTOR was direct target of miR101. MiR-101 mimics inhibited LPS-stimulated increase in the levels of IL-6, IL-1β and TNF-α in primary microglial cells in vitro. In the rat CCI model, miR-101 mimics also suppressed CCI-induced decrease in PWT and PWL and inhibited CCI-induced increase in mRNA and protein levels of IL-6, IL-1β and TNF-α. In addition, miR-101 downregulated mTOR mRNA and protein expressions in CCI rats. Besides, CCI operation resulted in miR-101 downregulation and mTOR mRNA upregulation in spinal microglia cells in a time-dependent manner. In conclusion, miR-101 had neuropathic pain-attenuating activity through targeting mTOR.

Additional file 1. Supplementary materials and methods. Subcellular fraction assay. The separation of cytoplasmic and nuclear fractions was performed using Nuclear and Cytoplasmic Extraction Reagents (Thermo Fisher Scientific, Wilmington, DE, USA) following the manufacturer’s protocols. Total RNA extracted from each fraction was used for detection of circNFIX and miR-378e by qRT-PCR assay. The relative expression levels of circNFIX and miR-378e in cytoplasmic and nuclear fractions were analyzed using GAPDH or U6 as cytoplasmic or nuclear control, respectively.

Objective We tested the hypothesis that low hemoglobin levels are associated with acute seizures after aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients with ruptured intracranial aneurysms were enrolled in the observational cohort study that prospectively collected age, sex, symptom onset, history of diabetes and hypertension, history of coronary artery disease, temperature, Hunt-Hess grade, Fisher grade, aneurysm location, hemoglobin, hematocrit, serum potassium, sodium, calcium, phosphorus, iron, and modified Rankin Scale. Acute seizures were determined as seizures within 1 week after aSAH. Results We included 554 patients with requisite data for analysis in the prospective study. Incidence of acute seizures following aSAH was 3.61%. In the univariate analysis, significant differences were detected in admission Hunt-Hess grade, Fisher grade, hemoglobin, and serum iron between epilepsy and nonepilepsy groups. Furthermore, acute seizures were associated with higher modified Rankin Scale score and poor outcome (P = 0.004). Serum hemoglobin levels were 114.30 ± 20.08 g/L in the epilepsy group, which were lower than those in the nonepilepsy group (128.64 ± 17.94 mmol/L, P = 0.001). Serum iron levels were 8.89 ± 5.03 g/L in the epilepsy group, which were also lower than those in the nonepilepsy group (13.71 ± 6.70 mmol/L, P = 0.002). The hemoglobin level was positively correlated with serum iron on admission (ρ = 0.321, P = 0.000). In the multivariate logistic regression model, lower hemoglobin was considered as an independent risk factor of acute seizures (odds ratio 4.286, 95% confidence interval 1.492–12.315, P = 0.007). The optimal cutoff value for hemoglobin level as a predictor for acute epilepsy after aSAH was determined as 119 g/L in the receiver operating characteristic curve (sensitivity was 75.00%, and specificity was 69.48%). Conclusions These data support the hypothesis that hemoglobin was inversely associated with acute seizures following aSAH.

Objective The underlying pathology of brain leading to cognitive impairment in Parkinson’s disease (PD) remains poorly understood. The aim of our study was to test the hypothesis that mild cognitive impairment (MCI) in PD may be related to atrophy of special gray matter regions. Methods High-resolution T1-weighted magnetic resonance images of the brains and comprehensive cognitive function tests were acquired in 37 PD patients and 21 healthy controls (HC) from September 2013 to October 2014. Patients were divided into two groups: PD with MCI (PD-MCI, n = 18) and PD with normal cognition (PDNC, n = 19). Gray matter density differences were analyzed using voxel-based morphometry (VBM). VBM and cognitive results, UPDRS scores and Hoehn–Yahr stages were compared between PD-MCI, PDCN and HC group, and correlation analyses were performed between those brain areas and cognition scores, UPDRS scores and disease duration, which showed significant group differences. Results The demographic data and motor severity among three groups were similar. However, comprehensive cognitive function results were more severe in PD-MCI than the other two groups. Compared to the HC group, the PDNC group showed reductions in gray matter density in frontal, temporal, parietal, bilateral insula lobes and many other regions of brain. Besides above changes, the PD-MCI group also revealed gray matter concentration decrease in left hippocampus and thalamus, and these changes still remained when compared with the PDNC group. The HC group did not show any more areas of atrophy in gray matter than others. Gray matter loss in PD represented significant correlations with global cognitive scores, motor severity or disease duration in some of these atrophic regions. Conclusion The initial stages of cognitive function decline in patients with PD is closely associated with gray matter atrophy in left hippocampus and thalamus. These two regions may serve as potential imaging biomarkers for PD-MCI.

It is not fully established whether leukocyte can predict the poor outcome for ruptured cerebral aneurysms (CA) or not. Here, we retrospectively analyzed the clinical data of 428 patients with ruptured CA between 2010 and 2015. Patients' demographic data, including gender, age, history of smoking, alcohol, hypertension, diabetes and hypercholesterolemia, Hunt-Hess and Fisher grade, occurrence of hydrocephalus, aneurysm location, time to surgery, delayed ischemic neurological deficit (DIND) and peak leukocyte of blood test from day 1 to 3 after aneurysmal rupture were recorded and analyzed. In the multivariable analysis model, gender, Fisher grade, time to surgery and hydrocephalus were not relevant to poor outcome. However, Hunt-Hess grade, DIND and preoperative leukocyte count (13.84 × 10

Background The pineal region tumors are surrounded by important structures. Neuroendoscopy has been increasingly used at home and abroad. This study is to simulate pure neuroendoscopic infratentorial supracerebellar approach for resection of pineal region tumor from the cadaveric head, and discuss the advantages and safety through this corridor. Methods The anatomical structure for resection of pineal region tumor was visualized through pure neuroendoscopic infratentorial supracerebellar approach in three cadaveric heads. Three cases with pineal region tumors were retrospectively analyzed and summarized between June 2017 and December 2017. All cases were operated through pure neuroendoscopic infratentorial supracerebellar approach in the first affiliated hospital of Fujian medical university. Results The anatomical structures of pineal region can be completely visualized by pure neuroendoscopic infratentorial supracerebellar corridor in the cadaveric head. Among the three cases, the first case was total resection, the second case was subtotal resection and the last case was partial resection. The postoperative pathology revealed cavernous hemangioma, germinoma and yolk sac tumor, respectively. The patients were followed-up for 1–6 months and had normal life.The KPS (karnofsky performance status) score was 100. Conclusion The anatomical structure of the pineal region can be completely visualized and the tumor can be safely removed through pure neuroendoscopic infratentorial supracerebellar approach.

OBJECTIVEGlutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms.METHODSEndovascular perforation was performed to induce SAH in male Sprague-Dawley rats. ANXA7-siRNA was administered via intraventricular injection 5 days before SAH induction. Neurological test, evaluation of SAH grade, assessment of blood-brain barrier (BBB) permeability, measurement of brain water content, Western blot, double immunofluorescence staining, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA) were performed at 24 hours of SAH induction.RESULTSANXA7 protein expression increased significantly after SAH induction and was seen mainly in neurons. High expression of ANXA7 was associated with poor neurological status. ANXA7 knockdown dramatically ameliorated early brain injury through alleviating BBB disruption and brain edema. Further investigation of the mechanism showed that inhibiting ANXA7 expression can rescue neuronal apoptosis. In addition, ANXA7 knockdown also significantly reduced glutamate release, which was consistent with a significant increase of Bcl-2 expression and decreases of Bax and cleaved caspase-3 expression.CONCLUSIONSANXA7 can induce neuronal apoptosis by affecting glutamate release in rats with SAH. Downregulating the expression of ANXA7 can significantly attenuate early brain injury after SAH. Future therapy targeting ANXA7 may be a promising new choice.

Dysmorphic neurons and balloon cells constitute the neuropathological hallmarks of type II focal cortical dysplasias (FCDs) with refractory epilepsy. The genesis of these cells may be critical to the histological findings in type II FCD. Recent work has shown enhanced activation of the mTOR cascade in both balloon cells and dysmorphic neurons, suggesting a common pathogenesis for these two neuropathological hallmarks. A direct comparative analysis of balloon cells and dysmorphic neurons might identify a molecular link between balloon cells and dysmorphic neurons. Here, we addressed whether PDK1-AKT-mTOR activation differentiates balloon cells from dysmorphic neurons. We used immunohistochemistry with antibodies against phosphorylated (p)-PDK1 (Ser241), p-AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-P70S6K (Thr229), and p-p70S6 kinase (Thr389) in balloon cells compared with dysmorphic neurons. Strong or moderate staining for components of the PDK1-AKT-mTOR signaling pathway was observed in both balloon cells and dysmorphic neurons. However, only a few pyramidal neurons displayed weak staining in control group (perilesional neocortex and histologically normal neocortex). Additionally, p-PDK1 (Ser241) and p-AKT (Thr308) staining in balloon cells were stronger than in dysmorphic neurons, whereas p-P70S6K (Thr229) and p-p70S6 kinase (Thr389) staining in balloon cells was weaker than in dysmorphic neurons. In balloon cells, p-AKT (Ser473) and p-mTOR (Ser2448) staining was comparable with the staining in dysmorphic neurons. Our data support the previously suggested pathogenic relationship between balloon cells and dysmorphic neurons concerning activation of the PDK1-AKT-mTOR, which may play important roles in the pathogenesis of type II FCD. Differential expression of some components of the PDK1-AKT-mTOR pathway between balloon cells and dysmorphic neurons may result from cell-specific gene expression.

To study the anatomy and clinical application of monolateral pterional keyhole approaches for treating bilateral cerebral aneurysms.Twelve formalin-fixed cadaveric heads underwent right pterional keyhole approaches for management of simulative contralateral aneurysms. The length of the contralateral middle cerebral artery (MCA), distal internal carotid artery (DICA), anterior cerebral artery, and ophthalmic segment of the internal carotid artery (OICA) was recorded. The operability of contralateral aneurysms was assessed using a modified numeric grading system. A total of 16 patients (12 patients with ruptured aneurysms) with bilateral cerebral aneurysms undergoing contralateral pterional keyhole approaches were included.The contralateral A1 segment of the anterior cerebral artery, proximal A2 segment, M1 segment of the MCA, DICA, and OICA was exposed via pterional keyhole approaches. An additional 2 mm of the OICA was exposed after incision of the falciform dural fold was completed. Contralateral aneurysms of the M1 segment (posterior), M2 segment, MCA bifurcation (inferior), A2 segment (lateral), DICA (posterior and lateral), and OICA (superior, inferior, and lateral) could not be fully exposed to perform simulated surgical clipping (operability rate75%). A total of 36 aneurysms underwent adequate surgical clipping via unilateral pterional keyhole approaches, whereas 1 aneurysm of the A3 segment did not.Contralateral aneurysms of the M1 segment (anterior, superior, and inferior), MCA bifurcation (superior and lateral), A1 segment, A2 segment (anterior, posterior, and medial), internal carotid artery bifurcation, DICA (anterior and medial), and OICA (medial) were fully exposed from different angles and surgical maneuvers were performed via pterional keyhole approaches, including in patients presenting with subarachnoid hemorrhage.

Background The multi-target deep brain stimulation (DBS) aimed at improving symptoms related to different nuclei is a promising research direction. However, to implant a single lead into multiple targets simultaneously is difficult with the current lead implantation method. New method We proposed a novel stereotaxic system used for implanting a curved lead to any two targets of the brain, and used the theoretical “curved lead method”. First, a customized novel stereotaxic system was fabricated, and a solid cranial model with six fixed internal targets was made; second, CT scan was performed to locate the fixed internal targets; third, five curved leads were implanted to five selected pairs of targets, each following the calculated parameters of “curved lead pathway” with the novel stereotaxic system, respectively. Finally, CT scans were performed again to determine the exact locations of the curved leads. Results The five curved leads accurately passed through the five pairs of combined targets, respectively, and the average vector error of curved lead implantation was 0.70 ± 0.24 mm. Comparison with Existing Method(s) In most situations, performing a multiple-target DBS procedure with the current stereotaxic systems means increased number of implanted leads, increased incidence of operative complications, and increased medical costs. However, the novel stereotaxic system could guide a single lead to reach two selected targets of the brain with high accuracy. Conclusions The novel stereotaxic system enables curved lead implantation with high accuracy, and can be considered as a useful complement to the current stereotaxic system.

Neuroglobin (Ngb) overexpression is considered as an intrinsic neuroprotective response. Therefore, exogenous Ngb increased in brain tissues has become a promising therapeutic strategy for neurological diseases. Previous studies demonstrated that transactivator of transcription (TAT) protein transduction domain was able to mediate synthetic Ngb entrance into neurons, and then protected brain from hypoxia-ischemic injury. However, the role of recombinant Ngb on early brain injury following subarachnoid hemorrhage (SAH) has not been elucidated. The objectives of this study were to investigate the expression of endogenous Ngb in brain using a rabbit model of SAH, and to verify whether TAT-Ngb fusion protein could be delivered into brain parenchyma, as well as to explore the neuroprotective effect of Ngb and its possible mechanisms. We found that Ngb expressions were up regulated in the transcript and protein levels in a similar time dependent manner after SAH as compared to the sham group. Moreover, TAT-Ngb fusion protein was successfully generated and transferred into brain neurons. Compared with the saline- and Ngb-treated group, neuronal viabilities and neurological outcomes were significantly improved 72 h post-SAH in the TAT-Ngb-treated group. Likewise, anti-apoptotic Bcl-2 protein was also elevated obviously. Conversely, pro-apoptotic factors including caspase 3, caspase 9 and Bax were greatly decreased after TAT-Ngb treatment. Our results suggest that Ngb plays a neuroprotective effect in rabbits suffering from SAH possibly through inhibiting the SAH-induced activation of mitochondria apoptotic pathway. Furthermore, TAT-mediated Ngb delivery into brain may be a promising therapeutic approach.

Objective To seek a cerebral perfusion pressure (CPP) threshold that can reduce the occurrence of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Methods We analyzed the clinical data of patients with the diagnosis of aSAH and underwent CPP monitoring in our department from February 2014 to December 2015. CPP was divided into four specified thresholds by every 10 mmHg increments, which were from 50 mmHg to 80 mmHg. The totally time ratio of CPP below each threshold was calculated. The correlation between the time ratio and DCI were analyzed using binary logistic regression. And receiver operating characteristic curve was performed to identify the cutoff time ratios at higher risk of DCI. Results Finally, 17 patients developed DCI from 60 patients who were recruited. The time ratios of CPP which was below 50 mmHg, 60 mmHg and 70 mmHg were found predictors of DCI by the binary logistic regression. The cutoff time ratios were 0.4% (AUC = 0.777), 7.0% (AUC = 0.702), 28.7% (AUC = 0.696) respectively. While at the level of 80 mmHg, the cutoff time ratio was 65% (AUC = 0.595). It was not related to DCI (P = 0.167). Patients suffered from DCI had a worse outcome than who did not at 3 month after aSAH (P = 0.018). Conclusion Time ratios at higher risk of DCI had a positive relationship with the CPP thresholds. Keeping CPP above 70 mmHg may be helpful to prevent DCI after aSAH, but it still needs further investigation.

Deep brain stimulation is an effective way to treat movement disorders, and a powerful research tool for exploring brain functions. This report proposes a “curved lead pathway” method for lead implantation, such that a single lead can reach in sequence to any two intracranial targets. A new type of stereotaxic system for implanting a curved lead to the brain of human/primates was designed, the auxiliary device needed for this method to be used in rat/mouse was fabricated and verified in rat, and the Excel algorithm used for automatically calculating the necessary parameters was implemented. This “curved lead pathway” method of lead implantation may complement the current method, make lead implantation for multiple targets more convenient, and expand the experimental techniques of brain function research.

The basal ganglia-cortical circuits are important for information process to brain function. However, chronic recording of single-unit activities in the basal ganglia nucleus has not yet been well established. We present a movable bundled microwire array for chronic subthalamic nucleus (STN) single-unit electrocorticogram co-recording. The electrode assembly contains a screw-advanced microdrive and a microwire array. The array consists of a steel guide tube, five recording wires and one referenced wire which form the shape of a guiding hand, and one screw electrode for cortico-recording. The electrode can acquire stable cortex oscillation-driven STN firing units in rats under different behaving conditions for 8 weeks. We achieved satisfying signal-to-noise ratio, portions of cells retaining viability, and spike waveform similarities across the recording sections. Using this method, we investigated neural correlations of the basal ganglia-cortical circuits in different behaving conditions. This method will become a powerful tool for multi-region recording to study normal statements or movement disorders.

Objective The central mechanisms underlying postherpetic neuralgia (PHN) pain remains unknown. The primary purpose of this study was to identify microstructural white matter changes closely related to the PHN pain by means of diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) analysis. Methods DTI data of the brains were obtained from 8 PHN patients and 8 healthy controls (HC) that were matched in age, gender, and educational level. DTI metrics, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were separately compared between the two groups using TBSS analysis to detect subtle microstructural changes. Partial correlation analyses were also conducted to evaluate the association between the altered DTI measures and clinical features. Results Average diffusion indices of white matter skeletons in the whole-brain showed no significant difference between the two groups. However, compared to the HC group, patients with PHN pain revealed reductions in localized FA and AD values in white matter underlying insula, occipital lobe, cerebellum, precentral gyrus, and many other regions, but without distinct change in regional MD and RD levels. In addition, decline of FA and AD values in patients represented significant negative correlations with PHN pain duration when the effect of VAS scores were excluded. Conclusion The current study suggest that there exists altered microstructure integrity of white matter in multiple brain regions in patients with PHN, and these changes increase in size as the duration of the pain increases. These findings might provide a new insight into the mechanism of PHN pain in brain.

The development of three-dimensional (3D) printing technology provides a new method for surgical treatment, but currently there are few reports on its application in the treatment of aneurysm. The aim of the present study was to explore the materials and methods of fabricating 3D printed individual aneurysm model and its value in the treatment of intracranial aneurysm. Twenty-four patients with intracranial aneurysm diagnosed by CTA who had undergone operation in our hospital were analyzed retrospectively. CTA Data collected at the time of surgery was used for reconstruction. Soft Mimics 17.0 was used to reconstruct the thin layer CTA scan data into 3D image and the final data was sent to the 3D printer for fabricating the model. We compared the proposed 3D printed model-based preoperative plan and the actual approach used in the surgery based on CTA data to evaluate the value of the 3D printed model in preoperative planning, and picked out the materials which were more suitable for the clinic. Twenty-four aneurysm models with high degree of reality were fabricated successfully with 3D-printing technology. The patients’ blood vessels, skulls and aneurysms were printed into the reality model at a ratio of 1:1. It is reported that the soft material-based, 3D printed vascular and aneurysm model more closely resembled the characteristics of the real blood vessels, thus provides a better simulation compared to the plaster-based model. Compared with the original operation plan, 3D printed model could be used for pre-operative aneurysm clip selection, and provide more intuitive information in selection of operational approach. 3D printed model can be used as an operational physical model to design operative schemes, choose the best operative paths and select suitable aneurysm clips by its high simulation degree and individualized characteristics. The model is helpful for surgical planning, especially for the preoperative plan of treating refractory multiple aneurysms and giant aneurysms.

Background Neurophysiologic monitoring during surgery is to prevent permanent neurological injury resulting from surgical manipulation. To improve the accuracy and sensitivity of intraoperative neuromonitoring, combined monitoring of transcranial electrical stimulation motor evoked potentials (TES-MEPs), somatosensory evoked potentials (SSEPs) and brainstem auditory evoked potentials (BAEPs) was attempted in microsurgery for lesions adjacent to the brainstem and intracranial aneurysms. Methods Monitoring of combined TES-MEPs with SSEPs was attempted in 68 consecutive patients with lesions adjacent to the brainstem as well as intracranial aneurysms. Among them, 31 patients (31 operations, 28 of posterior cranial fossa tumors, 3 of posterior circulation aneurysms) were also subjected to monitoring of BAEPs. The correlation of monitoring results and clinical outcome was studied prospectively. Results Combined monitoring of evoked potentials (EPs) was done in 64 (94.1 %) of the 68 patients. MEPs monitoring was impossible for 4 patients (5.9%). No complication was observed during the combined monitoring in all the patients. In 45 (66.2%) of the 68 patients, EPs were stable, and they were neurologically intact. Motor dysfunction was detected by MEPs in 8 patients, SSEPs in 5, and BAEPs in 4, respectively. Conclusions A close relationship exists between postoperative motor function and the results of TES-MEPs monitoring. TES-MEPs are superior to SSEPs and BAEPs in detecting motor dysfunction, but combined EPs serve as a safe, effective and invasive method for intraoperative monitoring of the function of the motor nervous system. Monitoring of combined EPs during microsurgery for lesions adjacent to the brainstem and intracranial aneurysms may detect potentially hazardous maneuvers and improve the safety of subsequent procedures.

The aims of this study were to observe the differential expression of PI3K-AKT pathway-related genes in seizure-inducing brain lesions in type II focal cortical dysplasia, and to explore the relationship between gene expression and histological changes in dysplastic foci and their epileptogenic mechanism. Typical lesions in brain tissue from three patients with epilepsy induced by type II focal cortical dysplasia were selected for analysis, along with normal brain tissue from two control group individuals. Following quantitative expression analysis using the RT2 Profiler(TM) PI3K-AKT PCR Array, differential expression of the pathway related genes was detected in the focal brain tissue lesions, and gene function queries were performed. Compared with the control group, thirteen related genes appeared to exhibit marked differences in expression in epileptic lesions from patients with type II focal cortical dysplasia; those genes were found to be involved in regulation of cell size, morphology, adhesion, migration, and apoptosis, and in immunity, inflammation, and many other domains. The differential expression of multiple genes in the PI3K-AKT signaling pathway in type II focal cortical dysplasia may be an important molecular mechanism underlying histological changes and recurrent seizures.