Serum lipid levels are associated with orthostatic hypotension in multiple system atrophy patients.

OBJECTIVES: Orthostatic hypotension (OH) is one of the most important autonomic features of multiple system atrophy (MSA). This study was established to confirm the correlation between lipid levels and OH in MSA. METHODS: A total of 580 patients with probable or possible MSA from neurological wards in six hospitals in Tianjin, Beijing, Hebei Province, and Henan Province, China, were included in this study. The tilt test or stand test was used to assess the severity of OH. Lipid contents, including total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglyceride were evaluated. RESULTS: Serum levels of total cholesterol, LDL-C, and triglyceride in MSA-OH patients were significantly lower than those in MSA without OH. The risks of OH were significantly higher in the lowest quartiles of triglyceride and LDL-C than in the highest quartiles, after adjusting for confounders (OR = 2.17, 95% CI: 1.23-3.82, P = 0.008 and OR = 2.02, 95% CI: 1.16-3.47, P = 0.012). The risk of severe OH was significantly higher in the lowest quartile and the second quartile of triglyceride than in the highest quartile after adjusting for confounders (OR = 2.16, 95% CI: 1.20-3.87, P = 0.010 and OR = 2.25, 95% CI: 1.24-4.07, P = 0.007). Moreover, the risk of OH was significantly higher in the lowest quartile, and the third quartile of TC than in the highest quartile after adjusting for confounders (OR = 2.04, 95% CI: 1.18-3.52, P = 0.010 and OR = 2.06, 95% CI: 1.19-3.56, P = 0.010). CONCLUSION: Low levels of TC, LDL-C, and triglyceride increased the risk of OH in MSA. A low level of triglyceride predicted severe OH in MSA.

White matter hyperintensities in cognitive impairment with Lewy body disease: a multicentre study.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with cognitive deficits and worse clinical outcomes in dementia, but rare studies have been carried out of cognitive impairment in Lewy body disease (CI-LB) patients. The objective was to investigate the associations between WMHs and clinical manifestations in patients with CI-LB. METHODS: In this retrospective multicentre cohort study, 929 patients (486 with dementia with Lewy bodies [DLB], 262 with Parkinson's disease dementia [PDD], 74 with mild cognitive impairment [MCI] with Lewy bodies [MCI-LB] and 107 with Parkinson's disease with MCI [PD-MCI]) were analysed from 22 memory clinics between January 2018 and June 2022. Demographic and clinical data were collected by reviewing medical records. WMHs were semi-quantified according to the Fazekas method. Associations between WMHs and clinical manifestations were investigated by multivariate linear or logistic regression models. RESULTS: Dementia with Lewy bodies patients had the highest Fazekas scores compared with PDD, MCI-LB and PD-MCI. Multivariable regressions showed the Fazekas score was positively associated with the scores of Unified Parkinson's Disease Rating Scale Part III (p = 0.001), Hoehn-Yahn stage (p = 0.004) and total Neuropsychiatric Inventory (p = 0.001) in MCI-LB and PD-MCI patients. In patients with DLB and PDD, Fazekas scores were associated with the absence of rapid eye movement sleep behaviour disorder (p = 0.041) and scores of Unified Parkinson's Disease Rating Scale Part III (p < 0.001), Hoehn-Yahn stage (p < 0.001) and the Montreal Cognitive Assessment (p = 0.014). CONCLUSION: White matter hyperintensity burden of DLB was higher than for PDD, MCI-LB and PD-MCI. The greater WMH burden was significantly associated with poorer cognitive performance, worse motor function and more severe neuropsychiatric symptoms in CI-LB.

Death-associated protein kinase 1 is associated with cognitive dysfunction in major depressive disorder.

We previously showed that death-associated protein kinase 1 (DAPK1) expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease. In addition, depression is a risk factor for developing Alzheimer's disease, as well as an early clinical manifestation of Alzheimer's disease. Meanwhile, cognitive dysfunction is a distinctive feature of major depressive disorder. Therefore, DAPK1 may be related to cognitive dysfunction in major depressive disorder. In this study, we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic, mild, unpredictable stressors. We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area, and tau was hyperphosphorylated at Thr231, Ser262, and Ser396 in these mice. Furthermore, DAPK1 shifted from axonal expression to overexpression on the cell membrane. Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction. These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.

The characteristic of nonmotor symptoms with different phenotypes and onsets in multiple system atrophy patients.

OBJECTIVES: The characteristic of nonmotor symptoms in patients with multiple system atrophy (MSA) has varied among previous studies. The objective was to investigatethe nonmotor characteristics in MSA patients with different phenotypes, sex and different onset patterns. METHODS: We performed a retrospective review of 1492 MSA patients. All cases were evaluatedby neurologists and assessed with motormanifestations, nonmotor symptoms, auxiliary examinationand brain MRI scans. RESULTS: Multiple system atrophy-cerebellar ataxia (MSA-C) was the predominant phenotype in 998 patients. Average age of onset (56.8 ± 9.2 years) was earlier, the disease duration (2.4 ± 2.2 year) was shorter and brain MRI abnormalities (49.2 %) were more frequently in MSA-C (P < 0.001). Multiple system atrophy-parkinsonism (MSA-P) patients were more likely to have nonmotor symptoms. After adjusted significant parameters, urinary dysfunction (OR 1.441, 95 %CI = 1.067-1.946, P = 0.017), constipation (OR 1.482, 95 %CI = 1.113-1.973, P = 0.007), cognitive impairment (OR 1.509, 95 %CI = 1.074-2.121, P = 0.018) and drooling (OR 2.095, 95 %CI = 1.248-3.518, P = 0.005) were associated with the MSA-P phenotype. Males were more likely to have orthostatic hypotension, urinary dysfunction, sexual dysfunction, drooling and females in constipation and probable RBD. In different onset patterns, constipation (59.2 %) and probable RBD (28.4 %) were more frequently in autonomiconset pattern. CONCLUSIONS: MSA-C is the predominant phenotype in Chinese patients, while many nonmotor symptoms are more common in MSA-P phenotype. Patients with different sex and onset patterns have different nonmotor characteristics. The different clinical features identified could help the physician counseling of MSA patients more easily and more accurately.

Costs of dementia with lewy bodies: A Chinese multicenter cross-sectional study.

INTRODUCTION: Dementia with Lewy bodies (DLB) significantly increases the economic burden on caregivers and society, but few studies have focused on the costs. This study aims to evaluate the current economic costs of DLB and its related factors. METHODS: A total of 193 patients diagnosed with probable DLB were consecutively enrolled from 6 memory clinics between August 2017 to July 2021. Data were collected from August to December of 2021, patients' per capita annual economic costs related to DLB in the year preceding the interview were evaluated, and factors related to the costs were assessed using regression analysis. RESULTS: Patients with DLB led to per capita annual total costs of US $21,378.3 in 2021, with direct medical costs, direct non-medical costs and indirect costs of US $3471.4, US $3946.4 and US $13,960.5, respectively, accounting for 16.2%, 18.5% and 65.3%, of total costs. Factors related to the costs of DLB showed that impairments in activities of daily living (ADL) and caregivers' subjective burden had a greater impact on the total, direct medical and indirect costs. CONCLUSION: The economic burden of DLB in China is huge, and indirect costs account for the largest proportion, serious impairment of the ADL and the subjective burden of caregivers, which possibly has a greater effect on costs. The substantial contributions made by family members and other unpaid caregivers of DLB should be fully recognized in strategic policy discussions and in case-level planning and assessments.

Sex differences in clinical cognitive impairment with Lewy bodies: a Chinese multicenter study.

BACKGROUND: Research on sex ratios of Lewy body dementia is controversial, established in small samples, and rarely focused on prodromal stage. The objective is to investigate the clinical sex ratios (men/women) and their associations with clinical features among individuals with mild cognitive impairment with Lewy bodies (MCI-LB), dementia with Lewy bodies (DLB), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) in China. METHODS: We conducted a multicenter cohort study, including 1038 individuals with probable MCI-LB, DLB, PD-MCI, or PDD diagnosis from 22 memory clinics in China from January 2018 to March 2022, and recorded their demographic and clinical data by reviewing medical records. Descriptive and regression analyses were used to calculate the sex ratio (men/women), and its associations with demographic and clinical data. RESULTS: In this study, men comprised 35.14% (men/women sex ratio = 0.54) for MCI-LB, 46.72% (men/women sex ratio = 0.88) for DLB, 63.56% (men/women sex ratio = 1.74) for PD-MCI, and 52.40% (men/women sex ratio = 1.10) for PDD. Sex ratios roughly increased with age. Men had more parkinsonism (p = 0.000) and less fluctuating cognition (p = 0.024) in MCI-LB, and those with PD-MCI had more RBD (p = 0.001). Women with PD-MCI had lower MMSE scores (ß ± standard error = - 1.24 ± 0.58, p = 0.04), more irritability (0.95 ± 0.46, p = 0.04) and fluctuating cognition (- 3.41 ± 1.31, p = 0.01), and less parkinsonism (- 2.10 ± 0.97, p = 0.03) than men after adjusting for demographic and cardiometabolic conditions. CONCLUSION: There were more women in DLB and MCI-LB, and more men in PD-MCI and PDD. The sex distribution, demographic, and clinical characteristics differed, which strengthened the independence and heterogeneity of the four diseases, and indicated sex-sensitive strategies for management of dementia necessary.

Temporal Variation in Disease Onset and Clinical Features of Lewy Body Disease in China.

BACKGROUND: Lewy body dementia is the second most common neurodegenerative dementia, but data concerning the onset age and clinical features in the prodromal stage remain limited in China. OBJECTIVE: To investigate the associations between onset age and clinical manifestations of cognitive impairment with Lewy bodies in a large-sample cohort. METHODS: We included 74 patients with mild cognitive impairment with Lewy bodies (MCI-LB), 533 patients with dementia with Lewy bodies (DLB), 118 patients with Parkinson's disease with MCI (PD-MCI), and 313 patients with Parkinson's disease dementia (PDD) in this multicenter cohort from 22 memory clinics of China from 1 January 2018 to 31 March 2022. The onset age, clinical manifestations, and neuropsychological assessments were recorded and analyzed after reviewing the medical records. RESULTS: The average onset age of memory loss was 68.28 (±7.00) years, and parkinsonism happened 2.00 (±1.24) years later for patients with MCI-LB. The average onset age of parkinsonism was 60.56 (±8.96) years, and the memory loss happened 3.49 (±3.02) years later for patients with PD-MCI. Rapid eye movement sleep behavior disorder and visual hallucinations were frequently reported in MCI-LB, DLB, and PDD, while visual hallucinations were least frequently reported in PD-MCI. Lower scores of MMSE and depression, and higher scores of activities of daily living and delusions, were independently associated with older onset age in DLB. CONCLUSION: The onset of PD-MCI precedes MCI-LB, and memory loss occurs 3 years after parkinsonism. The onset age is associated with cognition and neuropsychiatric symptoms in process.

Pisa syndrome in dementia with Lewy bodies: A Chinese multicenter study.

BACKGROUND: Pisa syndrome (PS) is rarely reported in Dementia with Lewy bodies (DLB). The aim of this article is to investigate the prevalence rate of PS and the correlation with clinical features evaluated in patients with DLB. METHODS: A total of 209 DLB patients were consecutively recruited and underwent standardized clinical evaluation in our multicenter study. The associations between PS and clinical factors were evaluated. RESULTS: The prevalence rate of PS in patients with DLB was 15.3%, which was higher in the moderate and severe stages than mild cognitive impairment and mild stages (81.2% vs. 18.8%). Patients with PS had a longer duration of disease (P = 0.020) and parkinsonism (P = 0.003), higher scores of NPI (P = 0.028), ADL (P = 0.002) and UPDRS part III (P < 0.001), lower scores of clock drawing test (P = 0.009), visuospatial/executive abilities (P = 0.018), attention (P = 0.020), language and praxis (P = 0.020), registration (P = 0.012), greater H&Y stage (P < 0.001), and higher proportion of cholinesterase inhibitors used (P = 0.044) than those without PS. Longer disease duration (OR = 1.166, P = 0.023), presence of parkinsonism (OR = 7.971, P = 0.007), moderate and severe dementia (OR = 3.215, P = 0.021) were associated with the presence of PS. Patients had a longer duration of PS (P = 0.014) and lower mean age of onset (P = 0.040) in the group with severe lateral trunk flexion. CONCLUSION: The development of PS may be associated with longer disease duration, the presence of parkinsonism and severe stages of dementia in DLB. Cholinesterase inhibitors may have a correlation with PS. The severity of lateral flexion is related to the duration of PS and mean age of onset.

Vascular, flow and perfusion abnormalities in Parkinson's disease.

BACKGROUND: Reduced flow into the brain or decreased jugular venous outflow from the brain may serve as a potential biomarker for Parkinson's disease (PD). Our goal was to compare the presence of vascular abnormalities, flow, and increases in midbrain iron content (a hallmark of the disease) in patients with PD. METHODS: A total of 85 PD patients and 85 healthy controls (HCs) were imaged at 3T. We assessed vascular abnormalities using magnetic resonance (MR) venography, average cerebral blood flow using 2D flow quantification, and substantia nigra iron content using susceptibility mapping. RESULTS: Fifty-two percent (52%) of the PD subjects showed venous structural and functional abnormalities in the two most severe categories, while ony 14% of the HC group showed these abnormalities. Total arterial flow (tA) was significantly lower for the PD group (10.9 ± 1.8 ml/s) compared to the HCs (11.6 ± 2.1 ml/s) (t = 2.28, p = 0.02). Of the PD patients (HCs), 42% (14%) had little flow on the left side. PD patients had higher heart rates and lower perfusion and the lower perfusion correlated with increased iron content in the substantia nigra. CONCLUSION: Some PD patients showed abnormal left internal jugular veins, lower tA, higher heart rates, and lower perfusion relative to HCs. These indicators could serve as early biomarkers for PD and create new avenues for future studies regarding the etiology of PD.

Down-regulation of taurine-up-regulated gene 1 attenuates inflammation by sponging miR-9-5p via targeting NF-κB1/p50 in multiple sclerosis.

AIMS: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by widespread inflammation. LncRNA taurine-up-regulated gene 1 (TUG1) has been reported to be involved in multiple biological processes and human diseases. The aim of this study was to investigate the role of lncRNA TUG1 in MS and the underlying mechanism. MAIN METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Lentiviral vectors encoding sh-TUG1 was constructed to silence TUG1 in MOG-EAE mice by intracerebroventricular (ICV) injection. The effect of TUG1 on inflammation in MS was evaluated by real-time PCR, Western blot, ELISA and Hematoxylin-eosin staining. To further study the mechanism of TUG1 in MS, TUG1 knockdown and miR-9-5p overexpression were performed in LPS-induced BV2 cells. KEY FINDINGS: Down-regulation of TUG1 improved mice behavior, reduced granulocyte-macrophage colony stimulating factor (GM-CSF) level, decreased the levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6 and IL-17, and increased IL-10 in EAE mice. Notably, TUG1 expression was negatively correlated with miR-9-5p expression, while positively correlated with NF-κB1/p50. Knockdown of TUG1 or enforced expression of miR-9-5p inhibited LPS-induced inflammation in BV2 cells, while these effects were abolished by inhibition of miR-9-5p. We further verified that TUG1 negatively regulated miR-9-5p expression and NF-κB1/p50 is a direct target of miR-9-5p. SIGNIFICANCE: Down-regulation of TUG1 attenuates MS through inhibition of inflammation by sponging miR-9-5p via targeting NF-κB1/p50, suggesting that TUG1 is a potential therapeutic target for MS treatment.

The Potential Protective Effect of Curcumin on Amyloid-ß-42 Induced Cytotoxicity in HT-22 Cells.

BACKGROUND: We aimed to investigate the effect and mechanism of curcumin (CUR) in Alzheimer's disease (AD). METHODS: Mouse hippocampal neuronal cell line HT-22 was treated with Aß1-42 and/or CUR, and then cell viability was evaluated by cell counting kit 8, Beclin-l level was detected using western blotting, and the formation of autophagosomes was observed by transmission electron microscopy (TEM). Furthermore, transcriptome sequencing and analysis were performed in cells with Aß1-42 alone or Aß1-42 + CUR. RESULTS: Aß1-42 treatment significantly inhibited cell viability compared with untreated cells (P < 0.01). After treatment for 48 h, CUR remarkably promoted cell viability compared with cell treated with Aß1-42 alone (P < 0.01). Compared with cells treated with Aß1-42 alone, the expression of Beclin-1 was slightly reduced in cells with combined treatment of Aß1-42 with CUR (P < 0.05). Consistently, TEM results showed that CUR inhibited the formation of autophagosomes in cells treated with Aß1-42. Furthermore, the protein-protein interaction network showed five key genes, including MYC, Cdh1, Acaca, Egr1, and CCnd1, likely involved in CUR effects. CONCLUSIONS: CUR might have a potential neuroprotective effect by promoting cell viability in AD, which might be associated with cell autophagy. Furthermore, MYC, Cdh1, and Acaca might be involved in the progression of AD.

TRPML1 Participates in the Progression of Alzheimer's Disease by Regulating the PPARγ/AMPK/Mtor Signalling Pathway.

BACKGROUND: TRPML1 is reported to be involved in the pathogenesis of Alzheimer's disease (AD) by regulating autophagy; however, the underlying mechanism is not completely clear. METHODS: We developed an APP/PS1 transgenic animal model that presents with AD. TRPML1 was also overexpressed in these mice. Protein expression levels were determined by Western blot. Morris water maze (MWM) and recognition tasks were performed to characterize cognitive ability. TUNEL assays were analysed for the detection of neuronal apoptosis. Primary neurons were isolated and treated with the vehicle, Aß1-42 or Aß1-42 + mTOR activator, as well as infected with the recombinant adenovirus TRPML1 overexpression vector in vitro. Cell viability was measured by the MTS assay, and lysosomal Ca2+ was also measured. RESULTS: In the APP/PS1 transgenic mice, TRPML1 was downregulated, the PPARγ/AMPK signalling pathway was activated, the mTOR/S6K signalling pathway was suppressed, and autophagic lysosome reformation (ALR)-related proteins were upregulated. TRPML1 overexpression or treatment with PPARγ and AMPK inhibitors or an mTOR activator reduced the expression levels of ALR-related proteins, rescued the memory and recognition impairments and attenuated neuronal apoptosis in mice with the APP/PS1 transgenes. In vitro experiments showed that TRPML1 overexpression or treatment with the mTOR activator propranolol attenuated the Aß1-42-suppressed cell viability and the Aß1-42-decreased lysosomal [Ca2+] ion concentration in primary neurons. TRPML1 overexpression or treatment with the mTOR activator propranolol also attenuated the Aß1-42-inhibited mTOR/S6K signalling pathway and the Aß1-42-induced ALR-related protein expression levels. CONCLUSION: TRPML1 is involved in the pathogenesis of AD by regulating autophagy at least in part through the PPARγ/AMPK/mTOR signallingpathway.

Curcumin Exerts Effects on the Pathophysiology of Alzheimer's Disease by Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression.

BACKGROUND: To validate our speculation that curcumin may ameliorate Alzheimer's disease (AD) pathogenesis by regulating PI(3,5)P2 and transient receptor potential mucolipin-1 (TRPML1) expression levels. METHODS: We developed an animal model presenting AD by APP/PS1 transgenes. The mouse clonal hippocampal neuronal cell line HT-22 was treated with amyloid-ß1-42 (Aß1-42). Curcumin was administrated both in vivo and in vitro. MTS assay was used to detect cell viability, and the lysosomal [Ca2+] ion concentration was detected. The number of autophagosomes was detected by the transmission electron microscopic examination. Illumina RNA-seq was used to analyze the different expression patterns between Aß1-42-treated cells without and with curcumin treatment. The protein level was analyzed by the Western blotting analysis. PI(3,5)P2 or TRPML1 was knocked down in HT-22 cells or in APP/PS1 transgenic mice. Morris water maze and recognition task were performed to trace the cognitive ability. RESULTS: Curcumin increased cell viability, decreased the number of autophagosomes, and increased lysosomal Ca2+ levels in Aß1-42-treated HT-22 cells. Sequencing analysis identified TRPLML1 as the most significantly upregulated gene after curcumin treatment. Western blotting results also showed that TRPML1 was upregulated and mTOR/S6K signaling pathway was activated and markers of the autophagy-lysosomal system were downregulated after curcumin use in Aß1-42-treated HT-22 cells. Knockdown of PI (3,5)P2 or TRPML1 increased the protein levels of markers of the autophagy-lysosomal system after curcumin use in Aß1-42-treated HT-22 cells, inhibited mTOR/S6K signaling pathway, increased the protein levels of markers of the autophagy-lysosomal system after curcumin use in APP/PS1 mice. Besides, knockdown of PI(3,5)P2 or TRPML1 reversed the protective role of curcumin on memory and recognition impairments in mice with APP/PS1 transgenes. CONCLUSION: To some extent, it suggested that the effects of curcumin on AD pathogenesis were, at least partially, associated with PI(3,5)P2 and TRPML1 expression levels.

Betulinic acid protects against cerebral ischemia/reperfusion injury by activating the PI3K/Akt signaling pathway.

Betulinic acid (BA), a naturally occurring pentacyclic lupane group triterpenoid, has been demonstrated to protect against ischemia/reperfusion-induced renal damage. However, the effects of BA on cerebral ischemia/reperfusion (I/R) injury remain unclear. Hence, this study was to investigate the effects of BA on oxygen and glucose deprivation/reperfusion (OGD/R) induced neuronal injury in rat hippocampal neurons. Our results showed that BA pretreatment greatly attenuated OGD/R-induced neuronal injury. BA also inhibited OGD/R-induced intracellular ROS production and MDA level in rat hippocampal neurons. Furthermore, the down-regulation of Bcl-2, up-regulation of Bax and the consequent activation of caspase-3 induced by OGD/R were reversed by BA pretreatment. Mechanistic studies demonstrated that BA pretreatment up-regulated the expression levels of p-PI3K and p-Akt in hippocampal neurons induced by OGD/R. Taken together, these data suggested that BA inhibits OGD/R-induced neuronal injury in rat hippocampal neurons through the activation of PI3K/Akt signaling pathway.

Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway.

Parkinson's disease (PD) is an age-related complex neurodegenerative disease that affects ≤ 80% of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It has previously been suggested that mitochondrial dysfunction, oxidative stress and oxidative damage underlie the pathogenesis of PD. Curcumin, which is a major active polyphenol component extracted from the rhizomes of Curcuma longa (Zingiberaceae), has been reported to exert neuroprotective effects on an experimental model of PD. The present study conducted a series of in vivo experiments, in order to investigate the effects of curcumin on behavioral deficits, oxidative damage and related mechanisms. The results demonstrated that curcumin was able to significantly alleviate motor dysfunction and increase suppressed tyrosine hydroxylase (TH) activity in the SNpc of rotenone (ROT)-injured rats. Biochemical measurements indicated that rats pretreated with curcumin exhibited increased glutathione (GSH) levels, and reduced reactive oxygen species activity and malondialdehyde content. Mechanistic studies demonstrated that curcumin significantly restored the expression levels of heme oxygenase-1 and NAD(P)H: quinone oxidoreductase 1, thus ameliorating ROT-induced damage in vivo, via the phosphorylation of Akt and nuclear factor erythroid 2-related factor 2 (Nrf2). Further studies indicated that the Akt/Nrf2 signaling pathway was associated with the protective role of curcumin in ROT-treated rats. Inhibiting the Akt/Nrf2 pathway using a lentiviral vector containing Nrf2-specific short hairpin RNA, or the phosphoinositide 3-kinase inhibitor LY294002, markedly reduced the expression levels of TH and GSH, ultimately attenuating the neuroprotective effects of curcumin against oxidative damage. These results indicated that curcumin was able to significantly ameliorate ROT-induced dopaminergic neuronal oxidative damage in the SNpc of rats via activation of the Akt/Nrf2 signaling pathway.

The Use of Solitaire AB Stents in Coil Embolization of Wide-Necked Cerebral Aneurysms.

BACKGROUND: The Solitaire AB stent is one of many assistant stents used for treating wide-necked cerebral aneurysm, and has been used since 2003. However, large sample studies on its safety and effectiveness are lacking. The objective of this study was to evaluate the effectiveness and safety of the Solitaire AB stent in the coil embolization of wide-necked cerebral aneurysms. METHODS: Retrospective review of the clinical and image data of 116 patients with wide-necked cerebral aneurysms who had been enrolled at six interventional neuroradiology centers from February 2010 to February 2014 and had been treated by coil embolization; in total, 120 Solitaire AB stents were used. The degree of aneurysm occlusion was examined using digital subtraction angiography (DSA) immediately after the procedure and during follow-up, and was graded using the modified Raymond classification. We also observed complications to evaluate the safety and effectiveness of this therapy. RESULTS: The 120 Solitaire AB stents (4 mm × 15 mm, four stents; 4 mm × 20 mm, 16 stents; 6 mm × 20 mm, 36 stents; 6 mm × 30 mm, 64 stents) were inserted to treat 120 wide-necked cerebral aneurysms. All stents were inserted successfully. DSA immediately post-surgery revealed 55 cases of complete occlusion, 59 cases of neck remnant, and six cases of aneurysm remnant. Perioperatively, there were four cases of hemorrhage and four cases of stent thrombosis. The follow-up spanned 3-37 months; of 92 patients examined by DSA at the 6-month follow up, 12 had disease recurrence. CONCLUSIONS: The Solitaire AB stent is effective with a good technical success rate and short-term effect for assisting coil embolization of wide-necked cerebral aneurysms.