Vinpocetine improves dyskinesia in Parkinson's disease rats by reducing oxidative stress and activating the Wnt/ß-catenin signaling pathway.

Parkinson's disease (PD) is the commonest neurodegenerative disorder. It reduces motor and cognitive function in patients. Vinpocetine (Vinp) has the effects of anti-inflammatory and antioxidant, and could improve cognitive function in patients. This study was aimed to investigating the therapeutic effects of Vinp on dyskinesia in a 6-Hydroxydopamine hydrobromide (6-OHDA)-induced PD rat model. We constructed a PD rat model by injecting 6-OHDA, and intervened with Vinp for 7 days. The motor function of the rats was evaluated by an open-field test and rotation test. Besides, H&E staining was applied to observe the changes of dopaminergic neurons in the striatum. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in the rat striatum were detected. We assessed the impact of Vinp on α-synuclein (α-Syn) and Wnt/ß-catenin signaling pathway-related molecules by western blot and qRT-PCR. Rats in the PD group showed reduced horizontal movement frequency and number of squares crossed, increased contact time and rotation frequency, and reduced number of dopaminergic neurons accompanied by severe morphological damage. Vinp treatment increased the horizontal movement frequency and number of squares crossed, reduced the contact time, and rotation frequency in PD rats. Also, Vinp downregulated α-Syn protein expression and MDA level, while upregulated SOD activity in the striatum of PD rats. Furthermore, Vinp treatment activated the Wnt/ß-catenin signaling pathway in the striatum of PD rats. In conclusion, Vinp improved the dyskinesia in 6-OHDA-induced PD rats by alleviating oxidative stress, and these effects may be associated with activating the Wnt/ß-catenin signaling pathway.

Correlation between Bispectral Index and Prognosis of Patients with Acute Cerebral Infarction.

INTRODUCTION: This study aimed to investigate the clinical value of bispectral index (BIS) monitoring in assessing the consciousness and prognosis of Acute Cerebral Infarction (ACI) patients. METHODS: In total, 64 patients who suffered from ACI with consciousness disturbance were enrolled in this study. Glasgow Coma Scale (GCS) was performed to evaluate the consciousness level of ACI patients, and BIS was used to monitor the depth of anesthesia and sedation. Then, patients were divided into good prognosis, poor prognosis and death groups according to Modified Rankin Score (mRS). Discrimination analysis of BIS values and GCS score for the prediction of prognosis was performed using the Receiver Operator Characteristic (ROC) curve. RESULTS: GCS score and BIS values showed statistically significant differences among the three groups. Spearman rank correlation analysis revealed a significant positive correlation between BIS values and GCS score, while BIS values was negatively related with mRS. The ROC curve of prognosis prediction showed strong prognostic power, with Area Under the Curves (AUCs) between 0.830 and 0.917. Moreover, the AUC of BISmean score was higher than that of BISmax, BISmin and GCS, and BISmean of 74 was the best cut-off point for good prognosis. CONCLUSION: BIS directly reflects the degree of consciousness disturbance in ACI patients, and thus accurately predicts the prognosis, indicating potential application values of BIS in clinical practice.

Correction to: Silencing RNF13 Alleviates Parkinson's Disease - Like Problems in Mouse Models by Regulating the Endoplasmic Reticulum Stress-Mediated IRE1α-TRAF2-ASK1-JNK Pathway.

A Correction to this paper has been published: https://doi.org/10.1007/s12031-020-01746-x.

Antidepressant functions of Jie Yu Chu Fan capsule in promoting hippocampal nerve cell neurogenesis in a mouse model of chronic unpredictable mild stress.

BACKGROUND: Depression is a major public health challenge that imposes a great societal burden. Depression has been attributed to the decreased level of neurotransmitters and brain-derived neurotrophic factor (BDNF) levels. Chinese herbal medicine Jie Yu Chu Fan (JYCF) capsule has been shown to be effective in the management of depression. However, the mechanism has yet to be determined. This study aimed to explore the activity of JYCF against depression by establishing a mouse model of chronic unpredictable mild stress (CUMS) with fluoxetine as the positive control drug. METHODS: The open field test, sucrose preference test, forced swim test, and tail suspension test were carried out to observe the behavioral changes of animals. The levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine, as well as their respective metabolic products 5-hydroxyindoleacetic acid, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid in the mouse hippocampi were quantified by high-performance liquid chromatography (HPLC). Cell proliferation and apoptosis, and early and mature nerve cells in the hippocampi were observed by immunofluorescence. Reverse transcription polymerase chain reaction was used to identify BDNF expression in the hippocampi. RESULTS: After 5 weeks of unpredictable stimulation, a CUMS mouse model was successfully obtained, as indicated by sharply decreased sucrose preference and locomotor activity, as well as an increased immobility time in the forced swim test. Our results demonstrated that treatment with JYCF (1 and 5 g/kg) and fluoxetine (20 mg/kg) dramatically reversed the behavioral abnormalities in CUMS mice. At 1 g/kg, JYCF significantly increased NE, DA, and HVA levels in the hippocampi of CUMS mice. JYCF up-regulated the mRNA expression of BDNF and promoted cell proliferation in hippocampi of CUMS mice. CONCLUSIONS: Our study demonstrated that JYCF exhibits antidepressant activity comparable to that of fluoxetine in CUMS mice. Moreover, the antidepressant-like activity of JYCF was shown to be mediated by enhancing hippocampal nerve cell neurogenesis through increasing the levels of monoamine neurotransmitters and BDNF expression.

Silencing RNF13 Alleviates Parkinson's Disease - Like Problems in Mouse Models by Regulating the Endoplasmic Reticulum Stress-Mediated IRE1α-TRAF2-ASK1-JNK Pathway.

The objective of this study was to understand if RNF13 can affect Parkinson's disease (PD) model mice by modulating the endoplasmic reticulum stress (ERS)-mediated IRE1α-TRAF2-ASK1-JNK pathway. C57BL/6 mice injected with MPTP to establish PD mice models were divided into Control, MPTP, MPTP + sh-RNF13, and MPTP + sh-NC groups. Rotarod, balance beam, and open-field tests were used to assess the behavioral changes of experimental mice. Immunofluorescence assay was used to determine TH-positive expression in substantia nigra, TUNEL staining to detect apoptosis, and Western blotting to measure the expression of IRE1α-TRAF2-ASK1-JNK pathway. Besides, SH-SY5Y cells treated with MPP+ were assigned into Control, MPP+, MPP+ + sh-RNF13, and MPP+ + sh-NC groups in vitro to detect cell viability, apoptosis and Ca2+ level. When compared with those Control mice, MPTP mice showed decreased retention time spent on rotarod performance and prolonged time on balance beam test, as well as evident reductions in floor plane (FP) movements, moving time, moving distance, and mean velocity in open-field test, which had an obvious increase of TUNEL-positive cells, significant decrease of TH-positive cells, and remarkable up-regulations of RNF13, p-IRE1α/IRE1α, TRAF2, ASK1, and p-JNK/JNK. Meanwhile, MPTP mice treated with sh-RNF13 were improved in all above indexes. In vitro, MPP+ treated SH-SY5Y cells had decreased cell viability and increased cell apoptosis, as well as the upregulated IRE1α-TRAF2-ASK1-JNK pathway proteins and Ca2+ level. RNF13 knockdown improved all above indexes in SH-SY5Y cells treated with MPP+. Silencing RNF13 can alleviate motor dysfunction and dopamine neuronal damage in PD mice by inhibiting ERS-mediated IRE1α-TRAF2-ASK1-JNK pathway.

[Relationship between serum level of uric acid and benign paroxysmal positional vertigo].

OBJECTIVE: To confirm the possible relationships between serum level of uric acid (UA) and benign paroxysmal positional vertigo (BPPV). METHODS: A total of 87 patients with BPPV and 36 age- and gender-matched control subjects were recruited from our hospital between July 1, 2013 and July 1, 2014. All patients underwent a complete audio-vestibular test battery, such as Dix-Hallpike maneuver for posterior semicircular canal and supine roll test for horizontal semicircular canal. All risk factors such as the histories of heart and cerebral vascular diseases, and routine hematological and biochemical analyses were analyzed between two groups. RESULTS: No significant inter-group differences existed in age, gender, histories of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, smoking or drinking (P > 0.05). No significant differences existed between systolic blood pressure, diastolic blood pressure, ejection fraction, whole blood count, lipid profile, homocysteine, prealbumin and blood urea nitrogen in patients with BPPV compared with controls (P >0. 05). However, the values of UA (267 ± 86 vs 325 ± 75) µmol/L, hemoglobin ale (5.6 ± 1. 4 vs 6.5 ± 1. 0)%, albumin (36 ± 4 vs 40 ± 4) g/L and creatinine (72 ± 20 vs 81 ± 22) µmol/L were much lower in patients with BPPV versus controls (P < 0. 05). According to multiple Logistic regression model, the lower levels of hemoglobin ale and albumin were independently associated with BPPV (P <0. 05) with the odds ratio of 1. 473 (95% CI 1. 066 - 2. 037) and 1. 162 (95% CI 1. 025 - 1. 318), respectively. However, the level of UA was not independently correlated with the occurrence of BPPV [OR = 1. 005 (95% CI 1. 000 - 1. 011), P =0. 063]. CONCLUSION: The lower levels of hemoglobin alc and albumin are independently associated with BPPV. Although the value of UA is lower in patients with BPPV versus controls, it is not an independent risk factor for BPPV. Due to limited patient data, further studies are needed to clarify the association in a larger sample size of different ethnic groups or longer follow ups.

Myasthenia gravis and Guillain-Barré cooccurrence syndrome.

OBJECTIVE: The objective of this study was to review all cases in literature in which the clinical manifestations of myasthenia gravis (MG) and Guillain-Barré syndrome (GBS) were presented in the same patient including a new case of our own and identify the clinical characteristics and possible mechanisms of this syndrome. METHODS: We reviewed 12 reports in which 13 cases were diagnosed as MG and GBS. The clinical manifestations of the 13 cases and our new case were analyzed in detail to show the characteristics of this kind of syndrome. RESULTS: Of all the cases, 5 females and 9 males, 6 of them were Chinese; 3 were Americans; 3 were Israelis; 1 was white and one was a Frenchman. The age of seven patients was no more than 45 years old. They all had the symptoms of extrocular muscle weakness. Nerve conduction and RNS abnormal were seen in all tested cases. Acetylcholine receptor antibody was positive in all tested patients. Prognosis was good in 8 of the 11 recorded patients. CONCLUSIONS: Although extremely rare, MG and GBS may present in the same patient with variant characteristics. The typical clinical characteristics of GBS and MG may be helpful for the diagnosis of future possible cases.

Neurochemical correlates of cognitive dysfunction in patients with leukoaraiosis: a proton magnetic resonance spectroscopy study.

OBJECTIVES: Leukoaraiosis (LA) is a common radiological finding in the elderly and may reflect cerebral small vessel disease (SVD). Although SVD has been identified as a major cause of vascular cognitive impairment or vascular dementia, the mechanisms for this association remain unclear. We therefore aimed to measure brain metabolites in LA using proton magnetic resonance spectroscopy ((1)H-MRS) as to determine the relationship between cognitive function and neurochemical white matter profile. METHODS: We recruited 23 patients with LA and 23 age- and sex-matched healthy controls consecutively. Multi-voxel (1)H-MRS was performed with a volume of interest located in centrum semiovale that contained mainly white matter voxels. Three main ratios of N-acetyl aspartate (NAA)/Cr, choline (Cho)/Cr and NAA/Cho were obtained. Spearman rank correlation coefficients were calculated between the cognitive function and the measured metabolite ratios. RESULTS: We found significantly lower levels of NAA/Cho and NAA/Cr ratios in lesioned white matter in patients with LA than healthy controls (P<0.05). The ratios of NAA/Cho and NAA/Cr in normal appearing white matter (NAWM) were higher than lesioned white matter and lower than controls, but this difference was not significant (P>0.05). There was a positive relationship between Mini-Mental State Examination (MMSE) and NAA/Cho in NAWM (r = 0.417, P = 0.048), and also a positive relationship between MMSE and NAA/Cr in lesioned white matter (r = 0.551, P = 0.006) in patients with LA. A positive relationship between the Z scores of the executive function and NAA/Cho in lesioned white matter (r = 0.557, P = 0.006) was also found. CONCLUSION: The main finding of this study was a significant reduction in the ratios of NAA/Cr and NAA/Cho in lesioned white matter, which indicates a marker of neuronal loss or dysfunction in patients with LA, which was correlated with cognitive function. This relationship between cognitive function and metabolic changes suggests that (1)H-MRS can be explored as a marker for cognitive dysfunction in patients with LA.

[Correlates of cognitive impairment in patients with leukoaraiosis by magnetic resonance spectroscopy].

OBJECTIVE: To explore the pathological changes in patients with leukoaraiosis (LA) by magnetic resonance spectroscopy (MRS) and examine its relationship with cognitive function. METHODS: Twenty-three LA patients and 23 age and gender-matched healthy subjects were recruited from the Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between August 2010 and November 2010. All participants underwent the neuropsychological tests. Multi-voxel chemical shift imaging was performed and the regions of interest were positioned in bilateral frontal white matter. The relative metabolite ratios, involving N-acetyl aspartate/choline ratio (NAA/Cho), N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr), were estimated. The correlation of the MRS data and the performance of cognitive function was analyzed. RESULTS: The LA patients were associated with a worse performance of mini mental state examination (MMSE) versus the healthy controls (24 ± 3 vs 28 ± 1, P < 0.05). Univariate analysis of the MRS data revealed the ratios of NAA/Cho and NAA/Cr significantly decreased in bilateral frontal white matter lesions in the LA group versus the control group (1.72 ± 0.20 vs 1.96 ± 0.36, 1.67 ± 0.17 vs 1.85 ± 0.21, P < 0.05). The values of NAA/Cr and NAA/Cho in normal appearing white matter increased versus the LA group (1.83 ± 0.24 vs 1.72 ± 0.20, 1.78 ± 0.28 vs 1.67 ± 0.17) and decreased versus the control group (1.83 ± 0.24 vs 1.96 ± 0.36, 1.78 ± 0.28 vs 1.85 ± 0.21). But no significant differences were found (P > 0.05). The ratio of Cho/Cr did not differ among 3 groups (P > 0.05). The pathological change of NAA/Cr in white matter lesion in LA patients was markedly correlated with the performance of MMSE (r = 0.47, P < 0.05). CONCLUSION: NAA may be a marker of axonal loss/dysfunction in LA patients. And the changes of NAA/Cr have a positive correlation with cognitive impairment.

Genetic variants on chromosome 9p21 and ischemic stroke in Chinese.

In a hospital based case control study, we investigated the association of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, cyclin-dependent kinase inhibitor 2B (CDKN2B) gene, and two genetic variants (rs10757274 and rs2383206) on chromosome region 9p21 with ischemic stroke in Chinese Hans. Two polymorphisms in the CDKN2A gene (rs3088440 and rs3731245) and two polymorphisms in the CDKN2B gene (rs3217992 and rs1063192) were selected by using a strategy of tagging single nucleotide polymorphisms (tSNP). We observed significant association of rs2383206 with ischemic stroke. Subjects with the GG/GA genotype of rs2383206 had a 1.51-fold (95%CI 1.11-2.05, p=0.009) increased risk of stroke, compared with those with the AA genotype. In addition, the GG/GA genotypes of rs2383206 and rs3731245 was associated with an increased risk of large vessel subtype and small vessel subtype of ischemic stroke, respectively, with ORs of 2.09 (95%CI 1.30-3.37, p=0.002) and 1.63 (95%CI 1.06-2.51, p=0.026), respectively. In gene-environmental interaction analysis, elevation of ischemic stroke risk was observed among AG+GG genotype carriers who consume alcohol, smoke cigarette, and have hypertension, with adjusted combined ORs of 2.86(1.51-5.41), 4.30(2.38-7.77), and 13.97(7.78-25.07), respectively, compared with low-risk individuals for rs2383206 (GG carriers who did not consume alcohol, smoke cigarette, and without hypertension). We provide evidence that genetic variants on chromosome region 9p21 may implicated in the prevalence of ischemic stroke in Chinese.