Three Liquid-Liquid Phase Separation-Related Genes Associated with Prognosis in Glioma.

Purpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored. Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR. Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells. Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.

Melatonin Inhibits the Malignant Progression of Glioblastoma via Regulating miR-16-5p/PIM1.

OBJECTIVES: Melatonin (MT) is a pineal hormone with antineoplastic potential. This study aims to explore the therapeutic potential and mechanism of MT on glioblastoma (GBM). METHODS: A human GBM cell line, LN229, was used to evaluate the function of MT. Cell viability, apoptosis, and migration were detected by CCK-8, flow cytometry, and transwell assays, respectively. The mRNA and protein expressions of specific genes were measured by qRT-PCR and western blot, respectively. The regulatory relationship between miR-16-5p and PIM1 was validated by dual luciferase reporter gene assay. A mouse xenograft model was established to prove the anti-tumor effect and related mechanisms of MT in vivo. RESULTS: MT inhibited the viability and migration and promoted the apoptosis of LN229 cells in a dose-dependent manner. MiR-16-5p was dose-dependently up-regulated by MT in LN229 cells, negatively regulating its target PIM1. MiR-16-5p inhibitor eliminated the anti-tumor effect of MT in LN229 cells, while si-PIM1 reversed the effect of miR-16-5p inhibitor in MT-treated cells. MT inhibited the tumor growth in vivo and MT-induced PIM1 down-regulation was reversed by miR- 16-5p inhibition in tumor tissues. CONCLUSIONS: MT inhibits the malignant progression of GBM via regulating miR-16-5p-mediated PIM1.

The Exosomal MicroRNA Profile Is Responsible for the Mesenchymal Stromal Cell Transplantation-Induced Improvement of Functional Recovery after Stroke in Rats.

INTRODUCTION: The mechanism through which mesenchymal stromal cells (MSCs) enhance functional recovery in experimental models of stroke remains to be elucidated. This study was carried out to determine the microRNA (miRNA) profile elicited in response to MSC transplantation after stroke. METHODS: This was an in vivo study on the effect of MSC transplantation on the exosomal miRNA profile in a rat model of middle cerebral artery occlusion (MCAO)-induced stroke. Eighteen male Sprague-Dawley rats were subjected to MCAO surgery (model group), and half received a transplantation of MSCs (model + MSC group) isolated from rat bone marrow. A sham-operated group (Sham) was included as a control. After 7 days, the volume of the brain lesion and severity of the functional impairments were measured. Exosomes were isolated from blood plasma samples for miRNA transcriptome analysis by Illumina sequencing. RESULTS: The MCAO surgery successfully induced infarcts and neurological deficits in the rats, whereas the MSC transplantation significantly repaired these impairments. Illumina sequencing identified 764 known miRNAs, including 135 that were differentially expressed in common between the model + MSC and model, model and Sham, and model + MSC and Sham groups, respectively. Gene Ontology enrichment analysis revealed that the target genes of these miRNAs were associated with biological processes relevant to learning or memory and the development of the central and peripheral nervous systems. Pathway enrichment analysis identified a cluster of miRNAs (e.g., rno-miR-19b-3p, rno-miR-204-3p, rno-miR-125a-5p, rno-miR-672-3p, and rno-miR-667-3p) to be significantly related to the Janus kinase-signal transducer and activator of transcription, mechanistic target of rapamycin, phosphoinositide 3-kinases-Akt, and insulin signaling pathways via their control of their gene targets. CONCLUSION: We confirmed that MSC transplantation repaired stroke-induced functional impairments in rats by regulating various pathways associated with nervous system protection and MSC differentiation through the deregulation of exosomal miRNAs.

Exosomes derived from mesenchyml stem cells ameliorate oxygen-glucose deprivation/reoxygenation-induced neuronal injury via transferring MicroRNA-194 and targeting Bach1.

The neuroprotective function of miR-194 on neurovascular endothelial cell injury is perceived as a novel method for clinical therapy. So are exosomes (EXs), being attractive in neurofunctional recovery. However, whether EXs derived from mesenchymal stromal cells (MSCs) perform the same efficacy by transferring miR-194 and the underlying mechanism remain vague. This study rooted in oxygen-glucose deprivation/reoxygenation (OGD/R) model. MSCs were isolated by gradient centrifugation and identified by flow cytometry. EXs were obtained through ultracentrifugation, whereas protein levels of specific markers (CD63, TGS101), together with Bach1, Nrf2 and HO-1 were measured by western blot. The relative mRNA expressions of Bach1, NOX1, AGSL4, GPX4 and miR-194 were measured by RT-qPCR assays. Cell viability was measured by cell counting kit-8, and cell migration was detected by wound healing assay. The interaction between miR-194 and Bach1 was predicted by starBase and confirmed by dual luciferase reporter assay. OGD/R dampened cell viability and miR-194 expression. Bach1 could bind with miR-194. miR-194 mimic attenuated the effect of OGD/R on cell viability and protein levels of Nrf2, HO-1 and Bach1, whereas Bach1 overexpression reversed the effect of miR-194 mimics. MSC-EXs could merge with HBMECs. Based on this, MSC-EXs loaded with miR-194 downregulated Bach1 protein level and iron content and the mRNA expressions of NOX1 and ACSL4, yet upregulated miR-194 and GPX4 expressions and Nrf2/HO-1 protein level in OGD/R-injured cells, whereas those carrying ShmiR-194 had the opposite effects. Our study suggested MSC-EXs loaded with miR-194 attenuated OGD/R-induced injury via targeting Bach1, providing a new therapeutic strategy for cerebral injuries.

Neuroprotective Function of TNFAIP3 Interacting Protein 2 Against Oxygen and Glucose Deprivation/Reoxygenation-Induced Injury in Hippocampal Neuronal HT22 Cells Through Regulation of the TLR4/MyD88/NF-κB Pathway.

BACKGROUND: Tumor necrosis factor-α (TNF-α)-induced protein 3-interacting protein 2 (TNIP2) has been well demonstrated to act as a principal contributor to the development of inflammatory diseases; however, the role of TNIP2 in cerebral ischemic/reperfusion injury has never been studied. METHODS: Gene expression was examined by using quantitative real-time polymerase chain reaction and Western blot. The functional role of TNIP2 in oxygen and glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury was evaluated using cell counting kit-8, terminal deoxynucleotidyl transferase dutp nick end labeling assay and enzyme-linked immunosorbent assay. Commercial kits were applied to evaluate the activity of NF-kappa-B (NF-κB) and caspase-3, as well as the release of lactate dehydrogenase release (LDH). RESULTS: TNIP2 expression was substantially declined in HT22 cells following OGD/R stimulation. TNIP2 overexpression attenuated ODG/R-induced inflammation in HT22 cells, as evidenced by reduced levels of TNF-α, interleukin (IL)-1ß, and intercellular cell adhesion molecule-1 (ICAM-1), and increased levels of IL-10. TNIP2 overexpression also reduced activity of NF-κB under ODG/R condition. Meanwhile, OGD/R treatment caused a reduction of cell viability and an elevation of cell apoptosis in HT22 cells, as indicated by the increase in LDH and caspase-3 activity. Whereas, OGD/R-induced HT22 cell injury was mitigated by TNIP2 overexpression in HT22 cells. Besides, we found the involvement of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/NF-κB pathway in the neuroprotective effect of TNIP2 on OGD/R-induced HT22 cell damage. CONCLUSION: TNIP2 overexpression mitigates OGD/R-induced inflammatory response and apoptosis. Moreover, TLR4/MyD88/NF-κB pathway participates in the protective effect of TNIP2 on OGD/R-induced neuronal damage.

Curcumin promotes the proliferation, invasion of neural stem cells and formation of neurospheres via activating SDF-1/CXCR4 axis.

Curcumin is an active ingredient isolated from the rhizomes of Curcuma longa Linn with remarkably non-toxic bioavailability. This is an in vitro study. In this study, we explored the effects of curcumin on the proliferation, migration and neurogenesis of neural stem cells (NSCs). Primary NSCs were isolated from embryonic day 14 rats and then treated with curcumin and/or stromal derived factor-1 (SDF-1). NSCs showed an SDF-1-dependent proliferation and migration. Further results showed that curcumin and SDF-1 both promoted NSCs proliferation, migration and the formation of neurospheres. In addition, Curcumin up-regulated the expression of SDF-1 and promoted the formation of SDF-1/CXCR4 complex in NSCs. The western blot results showed that the phosphorylation levels of ERK, JNK, MAPK, NF-kB and Akt were up-regulated by curcumin. In contrast, the administration of CXCR4 inhibitor AMD3100 could offset the effect of curcumin. These results suggested that curcumin promoted the NSCs proliferation, migration and formation of neurospheres via SDF-1/CXCR4 in NSCs.

Curcumin Alleviates Cerebral Ischemia-reperfusion Injury by Inhibiting NLRP1-dependent Neuronal Pyroptosis.

BACKGROUND: Cerebral ischemia-reperfusion injury is caused by a blood reperfusion injury in the ischemic brain and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. OBJECTIVE: Curcumin was reported to exert a good therapeutic effect on neural cells against ischemia- reperfusion injury, However, the mechanism is not clear. METHODS: In this study, Oxygen-Glucose Deprivation (OGD) model of fetal rat cerebral cortical neurons and the Middle Cerebral Artery Occlusion (MCAO) model of rats were employed to mimic cerebral ischemia-reperfusion injury in vitro and in vivo, respectively. RESULTS: We confirmed that curcumin has a promotive effect on neuronal proliferation and an inhibitory effect on neuronal pyroptosis. Furthermore, we found that curcumin could improve cerebral infarction. The results of western blotting showed that curcumin down-regulated the expression of nucleotide-binding oligomerization domain-containing protein-, leucine-rich repeats-, and pyrin domain-containing protein 1 (NLRP1), cysteinyl aspartate-specific protease 1 (caspase-1), gasdermin D (GSDMD), IL-1ß, IL-6, TNF-α, and iNOS proteins in OGD and MCAO models. NLRP1- dependent neuronal pyroptosis played an important role in cerebral ischemia-reperfusion injury. CONCLUSION: Curcumin could effectively inhibit NLRP1-dependent neuronal pyroptosis by suppressing the p38 MAPK pathway and therefore exerted neuroprotective effects against cerebral ischemia- reperfusion injury.

Identification of inflammation­associated circulating long non­coding RNAs and genes in intracranial aneurysm rupture­induced subarachnoid hemorrhage.

Ruptured intracranial aneurysm (IA)­induced subarachnoid hemorrhage (SAH) triggers a series of immune responses and inflammation in the brain and body. The present study was conducted to identify additional circulating biomarkers that may serve as potential therapeutic targets for SAH­induced inflammation. Differentially expressed (DE) long non­coding RNAs (lncRNAs; DElncRNAs) and genes (DEGs) in the peripheral blood mononuclear cells between patients with IA rupture­induced SAH and healthy controls were identified in the GSE36791 dataset. DEGs were used for weighted gene co­expression network analysis (WGCNA), and SAH­associated WGCNA modules were identified. Subsequently, an lncRNA­mRNA regulatory network was constructed using the DEGs in SAH­associated WGCNA modules. A total of 25 DElncRNAs and 1,979 DEGs were screened from patients with IA­induced SAH in the GSE36791 dataset compared with the controls. A total of 11 WGCNA modules, including four upregulated modules significantly associated with IA rupture­induced SAH were obtained. The DEGs in the SAH­associated modules were associated with Gene Ontology biological processes such as 'regulation of programmed cell death', 'apoptosis' and 'immune response'. The subsequent lncRNA­mRNA regulatory network included seven upregulated lncRNAs [HCG27, ZNFX1 antisense RNA 1, long intergenic non­protein coding RNA (LINC)00265, murine retrovirus integration site 1 homolog­antisense RNA 1, cytochrome P450 1B1­AS1, LINC01347 and LINC02193] and 375 DEGs. Functional enrichment analysis and screening in the Comparative Toxicogenomics Database demonstrated that SAH­associated DEGs, including neutrophil cytosolic factor (NCF)2 and NCF4, were enriched in 'chemokine signaling pathway' (hsa04062), 'leukocyte transendothelial migration' (hsa04670) and 'Fc gamma R­mediated phagocytosis' (hsa04666). The upregulated lncRNAs and genes, including NCF2 and NCF4, in patients with IA rupture­induced SAH indicated their respective potentials as anti­inflammatory therapeutic targets.

Downregulation of hsa_circ_0000936 sensitizes resistant glioma cells to temozolomide by sponging miR-1294.

Glioma is one of the most aggressive forms of brain tumor and is hallmarked by high rate of mortality, metastasis and drug resistance. Herein, we explore the role of circular RNA (circRNA) hsa_circ_0000936 in the resistance of glioma cells to temozolomide (TMZ). In this study, Relative changes in gene expression levels were compared using qRT-PCR. The role of hsa_circ_0000936 was characterized by cell count kit -8 assay and flow cytometry. Luciferase reporter assay was carried out for target validation.We found that hsa_circ_0000936 was upregulated in glioma tissues as compared to their adjacent normal tissues. Increased expression of hsa_circ_0000936 was found in the glioma tissues of patients showing resistance to TMZ compared with that of patients showing sensitivity to TMZ. The upregulation of hsa_circ_0000936 was also confirmed in TMZresistant glioma cells. miR-1294 was downregulated in TMZ-resistant glioma cells and identified as a direct target of hsa_circ_0000936. Downregulation of hsa_circ_0000936 increased the sensitivity of TMZ-resistant glioma cells towards TMZ. Moreover, restoration of miR-1294 could abrogate the promoting effect of hsa_circ_0000936 on TMZ resistance in TMZ-resistant glioma cells. In conclusion, downregulation of hsa_circ_0000936 sensitizes TMZ-resistant glioma cells to TMZ by sponging miR-1294, suggesting that hsa_circ_0000936 may be a potential target for overcoming the resistance of glioma cells to TMZ.

Long non-coding RNA NCK1-AS1 promotes the tumorigenesis of glioma through sponging microRNA-138-2-3p and activating the TRIM24/Wnt/ß-catenin axis.

BACKGROUND: Glioma is a common brain malignancy with high mortality. The competing endogenous RNA (ceRNA) networks may play key roles in cancer progression. This study was conducted to probe the role of long noncoding RNA (lncRNA) NCK1-AS1 in glioma progression and the involved mechanisms. METHODS: Microarray analyses were performed to explore the lncRNAs/miRNAs/genes with differential expression in glioma. NCK1-AS1 levels in glioma tissues and normal brain tissues, and in glioma cell lines and normal human glial cells were identified. The interactions among NCK1-AS1, miR-138-2-3p and TRIM24 were validated through luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Gain- and loss-of functions of NCK1-AS1, miR-138-2-3p and TRIM24 were performed to identify their roles in the behaviors of glioma cells. The activity of the Wnt/ß-catenin pathway was measured. In vivo experiments were performed as well. RESULTS: High expression of NCK1-AS1 was found in glioma tissues and cells, especially in U251 cells. Online predictions and the integrated experiments identified that NCK1-AS1 elevated the TRIM24 expression through sponging miR-138-2-3p, and further activated the Wnt/ß-catenin pathway. Artificial silencing of NCK1-AS1 or up-regulation of miR-138-2-3p led to inhibited proliferation, invasion and migration but promoted cell apoptosis of U251 cells, while up-regulation of TRIM24 reversed these changes, and it activated the Wnt/ß-catenin pathway. The in vitro results were reproduced in in vivo experiments. CONCLUSIONS: Our study suggested that NCK1-AS1 might elevate TRIM24 expression and further activate the Wnt/ß-catenin pathway via acting as a ceRNA for miR-138-2-3p. Silencing of NCK1-AS1 might inhibit the progression of glioma.

Knockdown of circular RNA CEP128 suppresses proliferation and improves cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p.

BACKGROUND: Circular RNAs serve as key players in the development of tumorigenesis and chemoresistance. Circular RNA CEP128 has been reported to be involved in the development of chemoresistance. However, the role of circular RNA CEP128 in the resistance of glioma cells to temozolomide has not yet been characterized. METHODS: The expression of circular RNA CEP128, miR-145-5p, and ATP-binding cassette super-family G member 2 was evaluated using quantitative real-time PCR and western blot. The effects of circular RNA CEP128 on glioma cell proliferation and chemoresistance were evaluated by cell count kit-8 assay and colony formation assay. Luciferase reporter assay was performed for target validation. RESULTS: Circular RNA CEP128 was upregulated in glioma tissues and cell lines. Moreover, circular RNA CEP128 expression was higher in temozolomide-resistant glioma cells compared with that in their parental cells. Knockdown of circular RNA CEP128 inhibited cell proliferation, reduced the expression of ATP-binding cassette super-family G member 2, as well as reduced resistance to temozolomide in glioma cells. Additionally, miR-145-5p was underexpressed in glioma cells as well as temozolomide-resistant glioma cells. Also, miR-145-5p was identified as a target of circular RNA CEP128. Overexpression of miR-145-5p inhibited the proliferation of U251/temozolomide cells and reduced the expression of ATP-binding cassette super-family G member 2, however, these changes induced by miR-145-5p overexpression were blocked by circular RNA CEP128 overexpression. CONCLUSION: Knockdown of circular RNA CEP128 suppresses cell proliferation and improves the cytotoxic efficacy of temozolomide in glioma cells by regulating miR-145-5p, suggesting that circular RNA CEP128 might be a promising target for overcoming the resistance of glioma cells to temozolomide.

Mechanical Thrombectomy with Intraoperative Local Thrombolysis Versus Mechanical Thrombectomy with Continuous Thrombolysis for Treatment of Cerebral Venous Sinus Thrombosis: A Systematic Review of 82 Cases.

OBJECTIVE: The first-line treatment of cerebral venous sinus thrombosis (CVST) is systemic anticoagulation. However, patients with severe or a clinically worsening condition might benefit from mechanical thrombectomy (MT) combined with intraoperative thrombolysis (IOT) or MT with continuous thrombolytic infusion (CTI). The present study compared the efficacy and safety of these 2 endovascular therapeutic methods by performing a systematic review of the literature. METHODS: The present systematic review was conducted to identify all cases of CVST treated with MT+IOT or MT+CTI/MT+IOT+CTI reported in PubMed and Ovid. The recanalization rates, outcomes, operation-related complications, sequelae, and postoperative hemorrhage rates were evaluated. RESULTS: A total of 28 studies, including 82 patients, met the inclusion criteria. Alone, MT+IOT was performed in 42 patients (51%), and MT+CTI/MT+IOT+CTI was performed in 40 patients (49%). Overall, outcomes data were available for 69 patients, of whom 57 (82%) had had a good outcome and 12 (18%) had had a poor outcome or had died. Recanalization data were available for 68 patients. Of these patients, 28 (41%) had had complete recanalization, 40 (59%) had had partial, and no patient had had no recanalization. Operation-related complications occurred in 5 patients (6%), and 3 patients (4%) developed postoperative intracerebral hemorrhage. However, no significant differences were found in the recanalization rate or prognosis between the MT+IOT and MT+CTI/MT+IOT+CTI groups. CONCLUSIONS: The results from our review suggest that MT with local thrombolysis is relatively safe, with no significant differences in efficacy and safety between MT+IOT alone and MT+CTI/MT+IOT+CTI. However, randomized controlled studies are required to provide a definitive answer on its use for CVST.

Association between the polymorphism (rs17222919, -1316T/G) of 5-lipoxygenase-activating protein gene (ALOX5AP) and the risk of stroke: A meta analysis.

BACKGROUND: The objective of this study was to evalutate the relationship between 5-lipoxygenase-activating protein gene (ALOX5AP) -rs17222919-1316T/G polymorphisms and the risk of stroke. METHODS: Relative studies were searched in January 2018. Case-control studies with extractable data were selected. Four gene models were analyzed including, allele genetic model (G vs T), additive genetic model (GG vs TT, GT vs TT), recessive genetic model (GG vs GT + TT), and dominant genetic model (GG + GT vs TT). Effect sizes included odds ratio (OR) and 95% confidence interval (CI). Heterogeneity was assessed by using Q test and I test. Publication bias was evaluated by using Egger method. The reliability of the results was assessed with sensitivity analysis. All the data analysis was performed with R 3.10 software. RESULTS: A total of 5 studies inclusing 8492 patients were included. There were significant relationship between ALOX5AP-rs17222919-1316T/G polymorphisms and stroke under all models (P < .05) except the additive genetic model GT versus TT (P > .05). No publication bias was noted. Sensitivity analysis indicated that the results were not stable. CONCLUSION: This meta-analysis indicates that ALOX5AP-rs17222919-1316T/G may be a protective factor aginst stroke.

Neuroprotective Effect of Curcumin Against Cerebral Ischemia-Reperfusion Via Mediating Autophagy and Inflammation.

Curcumin, a polyphenolic compound extracted from Curcuma longa, has drawn attention for its effective bioactivities against ischemia-induced injury. This study aimed to evaluate the neuroprotective effect of curcumin and investigate the underlying mechanism that mediates autophagy and inflammation in an animal model of middle cerebral artery occlusion (MCAO) in rats. Curcumin was delivered to Sprague Dawley male rats at a dose of 200 mg/kg curcumin by intraperitoneal injection 30 min after ischemia-reperfusion (I/R). LY294002, a specific inhibitor of the PI3K/Akt/mTOR pathway, as well as anisomycin, an activator of TLR4/p38/MAPK, was administered by ventricle injection 30 min before MCAO. The same volume of saline was given as a control. Brain infarction and neurological function were determined 24 h post-MCAO. Immunoblotting and immunofluorescence were used to detect alterations in autophagy-relevant proteins Akt, p-Akt, mTOR, p-mTOR, LC3-II, and LC3-I, and inflammation-related proteins TLR4, p-38, p-p38, and IL-1 in the ipsilateral hemisphere. Cerebral I/R injury resulted in significant alterations of LC3-II/LC3-I, IL-1, TLR4, and p-p38. Curcumin in MCAO rats significantly improved brain damage and neurological function by upregulating p-Akt and p-mTOR and downregulating LC3-II/LC3-I, IL-1, TLR4, p-38, and p-p38. However, these protective effects against ischemia could be suppressed when LY294002 or anisomycin was included. Curcumin exerts neuroprotective effects by attenuating autophagic activities through mediating the PI3K/Akt/mTOR pathway, while also suppressing an inflammatory reaction by regulating the TLR4/p38/MAPK pathway. Furthermore, this study indicates that curcumin could be an effective therapy for patients afflicted with ischemia.

[Brain Protection of Muscone in Rats with Brain Injury].

OBJECTIVE: To observe cerebral protective effect of muscone (nasal administration) on traumatic brain injury model rats. METHODS: SD rats were divided into the sham-operation group, the model group, and the treatment groups according to random digit table, 50 in each group. Traumatic brain injury model was established by controlled cortical strike. Rats in the sham-operation group received surgery and anesthesia procedures only, with no strike. Muscone (1.8 mg/kg) was delivered to rats in the treatment group using in situ nasal perfusion, 30 min each time, twice daily for 7 successive days. Water content of brain tissue was detected in each group before intervention (T1), at day 3 of intervention (T2), day 5 of intervention (T3), and after intervention (T4), respectively. Expression levels of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detected using immunohistochemical analysis. RESULTS: Compared with the sham-operated group, water content of brain tissue increased (P < 0.05), and expression levels of NGF and BDNF decreased in the model group at T1, T2, T3, and T4 (P <0. 01). Compared with the model group, water content of brain tissue decreased (P < 0.05), and expression levels of NGF and BDNF increased (P < 0.01) in the treatment group at T1, T2, and T3. CONCLUSION: Nasal administration of muscone could reduce water content of brain tissue, alleviate cerebral edema, promote secretion of BDNF and NGF by olfactory ensheathing cells in traumatic brain injury rats.

[Treatment of Idiopathic Normal-Pressure Hydrocephalus by Wuling Powder Combined Ventriculo- peritoneal Shunt Surgery: an Efficacy Observation].

Objective To observe the clinical efficacy of Wuling Powder (WP) combined ventricu- loperitoneal shunt surgery in patients with idiopathic normal-pressure hydrocephalus (INPH). Methods Totally 56 INPH patients were randomly assigned to the control group and the treatment group, 28 in each group. All patients received ventriculoperitoneal shunt surgery. Three days after surgery patients in the treatment group took WP, while those in the control group took placebo decoction (one dose per day, once in the morning and once in the evening, 7 days as one course, a total of 6 courses after surgery). Mini- Mental State Examination (MMSE) score, the steps to turn around 180°, and Evan's index were tested be- fore surgery and 3 months after surgery. Adverse reactions were recorded in the two groups. Clinical effica- cy was assessed after 3 months of surgery. Results At month 3 after surgery 21 patients (80. 8%) were cured and 3 patients (11. 5%) were improved in the treatment group, with statistical difference when com- pared with the control group [14 cured (51. 9%) and 11 improved (40. 7%) ; P <0. 05]. Compared with be- fore surgery in the same group, levels of MMSE score increased and the steps to turn around 1800 were obviously reduced in the two groups at month 3 after surgery (both P <0. 05). Compared with the control group at month 3 after surgery, levels of MMSE score increased and the steps to turn around 1800 were ob- viously reduced in the treatment group (both P <0. 05). Conclusion In treating INPH patierts, WP com- bined ventriculoperitoneal shunt surgery was superior to the effect of using ventriculoperitoneal- shunt sur- gery alone.

Prognostic value of leptin: 6-month outcome in patients with intracerebral hemorrhage.

Leptin has recently been discussed as a novel biomarker for the clinical outcome of critical illness. This study aims to investigate the prognostic value of leptin with regard to long-term clinical outcomes in patients with intracerebral hemorrhage. In 50 healthy controls and 92 patients with acute spontaneous basal ganglia hemorrhage presenting to the emergency department of a large primary care hospital, we measured plasma leptin levels using an enzyme-linked immunosorbent assay in a blinded fashion. Plasma leptin levels on admission were considerably higher in patients than healthy controls. A significant correlation emerged between plasma leptin level and National Institutes of Health Stroke Scale score. A multivariate analysis identified plasma leptin level as an independent predictor for 6-month clinical outcomes including 6-month mortality and unfavorable outcome (Modified Rankin Scale score>2). Using receiver operating characteristic curves, we calculated areas under the curve for 6-month clinical outcomes. The predictive performance of leptin was similar to, but did not obviously improve that of National Institutes of Health Stroke Scale scores. Thus, leptin may help in the prediction of 6-month mortality and unfavorable outcome after intracerebral hemorrhage.

Copeptin is associated with one-year mortality and functional outcome in patients with acute spontaneous basal ganglia hemorrhage.

High plasma copeptin levels have been found to be associated with short-term poor outcome after intracerebral hemorrhage (ICH). We furthermore evaluate the relation of plasma copeptin levels to long-term outcome and early neurological deterioration after ICH. Fifty healthy controls and 89 patients with acute spontaneous basal ganglia hemorrhage were recruited in this study. Plasma copeptin concentrations on admission measured by enzyme-linked immunosorbent assay were considerably high in patients than healthy controls. A multivariate analysis identified plasma copeptin level as an independent predictor for 1-year mortality, 1-year unfavorable outcome (modified Rankin Scale score>2) and early neurological deterioration. A receiver operating characteristic curve showed that the predictive value of plasma copeptin concentration was similar to that of National Institutes of Health Stroke Scale scores for long-term poor outcome and early neurological deterioration. However, copeptin did not obviously improve the predictive values of National Institutes of Health Stroke Scale scores. Thus, increased plasma copeptin level is an independent prognostic marker of 1-year mortality, 1-year unfavorable outcome and early neurological deterioration after ICH.