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Purpose@#Ischemic brain injury results in high mortality and serious neurologic morbidity. Here, we explored the role of SNHG15 in modulating neuronal damage and microglial inflammation after ischemia stroke. @*Materials and Methods@#The hypoxia/ischemia models were induced by middle cerebral artery occlusion in mice and oxygenglucose deprivation/reoxygenation (OGD/R) in vitro. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to determine the levels of SNHG15, miR-302a-3p, and STAT1/NF-κB. Moreover, gain- or loss-of functional assays of SNHG15 and miR-302a-3p were conducted. MTT assay was used to evaluate the viability of HT22 cells, and the apoptotic level was determined by flow cytometry. Furthermore, enzyme-linked immunosorbent assay was performed to detect oxidative stress and inflammatory mediators in the ischemia cortex and OGD/R-treated BV2 microglia. @*Results@#The SNHG15 and STAT1/NF-κB pathways were both distinctly up-regulated, while miR-302a-3p was notably down-regulated in the ischemia cortex. Additionally, overexpressing SNHG15 dramatically enhanced OGD/R-mediated neuronal apoptosis as well as the expression of oxidative stress and inflammation factors from microglia. In contrast, knocking down SNHG15 or overexpressing miR-302a-3p relieved OGD/R-mediated neuronal apoptosis and microglial activation. Moreover, the rescue experiment testified that overexpressing miR-302a-3p also attenuated SNHG15 up-regulation-induced effects. In terms of the mechanisms, SNHG15 sponged miR-302a-3p and activated STAT1/NF-κB as a competitive endogenous RNA, while miR-302a-3p targeted STAT1 and negatively regulated the STAT1/NF-κB pathway. @*Conclusion@#SNHG15 was up-regulated in the hypoxia/ischemia mouse or cell model. The inhibition of SNHG15 ameliorates ischemia/hypoxia-induced neuronal damage and microglial inflammation by regulating the miR-302a-3p/STAT1/NF-κB pathway.
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Objective To explore the characteristics and influencing factors of cognitive dysfunction in patients with essential tremor (ET).Methods We recruited ET patients diagnosed by the Department of Neurology of the First Affiliated Hospital of Xi`an Jiaotong University and healthy volunteers who matched the ET patients in age, gender and education level for the study.We recorded all the patients` demographic information, tremor degree, and family history based on the family tree.All the participants were tested by MMSE, MoCA, ADL, HAMD and HAMA.Results There were 88 ET patients and 63 normal subjects included in the study.According to MMSE, 31.82％ of the patients had cognitive dysfunctions, with orientation, short-term memory, calculation ability, language skills, retelling, reading comprehension, three-level command and drawing being significantly lower than those of the healthy volunteers (P<0.01);orientation was the most serious damage in cognitive function domain (K=0.624, S=0.726);three-level command was the least serious damage (K=0.274, S=0.319).According to MoCA, 86.36％ of the ET patients had cognitive dysfunction higher than normal people (P<0.05);visual space and execution, clock drawing task, naming, attention, 100-7, language skills, abstract thinking and orientation were significantly lower than normal people (P<0.01);the most serious damage in cognitive function domain was visual space and execution (K=0.651, S=0.786); the least serious damage cognitive function domain was “100-7” (K=0.406, S=0.484). Education level and age affected cognitive dysfunction (P<0.05). ADL scores showed negative correlation with cognitive function (correlation =－0.375 and －0.383, respectively; P<0.001). After the effects of anxiety and depression were excluded, onset age and tremor grading were correlated with cognitive dysfunction (P<0.05). When the above factors were put into binary Logistic regression model, education level was found to be contributed to the model (P<0.05).Conclusion Patients with ET widely suffer from cognitive impairment. Age, education level, daily life disability, age of onset, and tremor degree classification can affect cognitive dysfunction.
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Objective To investigate the protection effect of cyclosporine A on spatial memory following chronic cerebral hypoperfusion in rats and its possible mechanism.Me,ods Sixty SD rats were randomly divided into sham operation,vehicle,low-dose cyclosporine A,medium-dose cyclosporine A,and high-dose cyclosporine A groups.A chronic cerebral hypoperfusion model was prepared by permanent bilateral ligation of bilateral common carotid arteries.From 46 days after modeling,olive oil 1 ml/d was used for intragastric administration in the sham-operation group and the vehicle group.Cyclosporine A 3 mg/kg,6 mg/kg,and 12 mg/kg were administrated intragastrically in the low-dose,medium-dose and high-dose cyclosporine A groups,respectively,once a day for 14 days.The spatial memory was assessed using Morris water maze test.Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of NADPH oxidase 4 (NOX4) mRNA in the cerebral cortex.Immunohistochemical staining and Western blot were used to detect the expression of NOX4 protein in the cerebral cortex.Results The Morris water maze test showed that the escape latencies in all cyclosporine A groups were significantly shorter than the vehicle group (all P ＜0.05).Immunohistochemical staining showed that the percentages of the NOX4-positive cells in the sham-operation,vehicle,low-dose,medium-dose,and high-dose cyclosporine A groups were4.43％ ±0.37％,37.44％ ±4.76％,18.05％ ±2.91％,12.51％ ±3.4％,and 11.06％ ±1.74％,respectively (F =262.021,P ＜ 0.001),the vehicle group was significantly higher than the sham-operation group (P ＜ 0.01),and all cyclosporine A groups were significantly less than the vehicle group (all P ＜ 0.01).RT-PCR showed that the expression levels of NOX4 mRNA in cerebral cortex in the sham-operation,vehicle,low-dose,medium-dose,and high-dose cyclosporine A groups were 0.36 ± 0.03,1.04 ± 0.04,0.58 ± 0.02,0.49 ± 0.01,and 0.40 ± 0.02,respectively (F =1 324.941,P ＜ 0.001),all cyclosporine A groups were significantly lower than the vehicle group (all P ＜ 0.01).Western blot showed that the expression levels of NOX4 protein in cerebral cortex in the sham-operation,vehicle,low-dose,medium-dose,and high-dose cyclosporine A groups were 0.02 ± 0.01,0.27 ± 0.04,0.09 ± 0.02,0.06 ± 0.02,and 0.06 ± 0.01,respectively (F =222.692,P ＜ 0.001),all cyclosporine A groups was significantly lower than the vehicle group (all P＜0.01).Conclusion Cyclosporine A may improve spatial memory following chronic cerebral hypoperfusion in rats by down-regulation of NOX4.
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Objective To analyze the characteristics of the common first attack of headache in patients with cerebral venous sinus thrombosis (CVST). Methods The clinical data of 51 patients who were diagnosed as CVST with MR venography (MRV)or DSA were collected retrospectively. The patients were divided into either a acute group (≤3 week,n= 32)or a chronic group (>3 weeks, n=19). Results (1)The age of onset of symptoms in these patients was 20 to 40 years,and most of them were females. Of all the first symptoms,headache ranked first,accounting for 84. 3%(43/51 );headache only accounted for 52. 9%(27/51 ),headache with other symptoms (ophthalmic symptoms, hemiplegia,and aphasia,etc. )accounted for 31. 4%(16/51 ),and other symptoms such as epilepsy, paralysis,and ophthalmic symptoms accounted for 15. 7%(8/51). (2)The proportion of headache only as the first symptom in the acute group was higher than that in the chronic group (65. 6% vs. 31. 6%,P0. 05 ). Conclusion Young patients without previous history of migraine,especially women of childbearing age with sudden onset and progressive worsening headache,and the patients with idiopathic intracranial hypertension,CVST should be considered as an important possibility.
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Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P ＜ 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P ＜0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It suggests that the optimal concentration of sumatriptan significantly down-regulates CGRP over-expression via intracellular ERK1/2 and JNK signaling transduction pathways in TG after organ culture.
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The Chinese herbal medicine Tianma (Gastrodia elata) has been used for treating and preventing primary headache over thousands of years, but the exact pharmacological mechanism of the main bioactive ingredient gastrodin remains unclear. In present study, the effects of gastrodin on calcitonin gene-related peptide (CGRP) and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) expression were observed in rat trigeminal ganglion (TG) after in vitro organ culture to explore the underlying intracellular mechanism of gastrodin on primary vascular-associated headache. CGRP-immunoreactivity (CGRP-ir) positive neurons count, positive area, mean optical density and integrated optical density by means of immunohistochemistry stain were compared at different concentrations of gastrodin, which was separately co-incubated with DMEM in SD rat TG for 24 hours. Only at 5 or 10 mmol L(-1) concentration, gastrodin demonstrated significantly concentration-dependent reduction of CGRP-ir (+) expression and its action closed to 1.2 mmol L(-1) sumatriptan succinate. While at 2.5, 20, and 40 mmol L(-1) concentration, gastrodin did not show remarkable effects on CGRP-ir (+) expression. The optimal concentration of gastrodin (5 and 10 mmol L(-1)) similarly inhibited CGRP-mRNA expression level separately compared with 1.2 mmol L(-1) sumatriptan succinate and 10 micromol L(-1) flunarizine hydrochloride, which was quantitatively analyzed by real-time PCR (RT-PCR). pERK1/2 level was examined by Western blotting after co-cultured with optimal concentration of gastrodin and effective specific ERK1/2 pathway inhibitors PD98059, U0126. The result indicated that gastrodin significantly reduced pERK1/2 protein actions similarly to ERK1/2 pathway specific blockade. It suggests ERK1/2 signaling transduction pathway may be involved in gastrodin intracellular mechanism. This study indicates gastrodin (5 and 10 mmol L(-1)) can remarkably reduce CGRP-ir (+) neuron, CGRP-mRNA and pERK1/2 expression level in cultured rat TG, with its actions similar to the effective concentration of sumatriptan succinate, flunarizine hydrochloride and specific ERK1/2 pathway blocker. The intracellular signaling transduction ERK1/2 pathway may be involved in the gastrodin reducing CGRP up-regulation in rat TG after organ culture.
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Objective To study the early diagnostic value of olfactory function measurement to Alzheimer disease (AD). Method Detected the thresholds of detectability, identification threshold with pictu.re-based odor identification test in 21 AD patients (AD group) and 21 healthy elderly people (control group), and evaluated the relationship with mini-mental state examination (MMSE). Results AD group was impaired on threshglds of detectability [(1.81±0.75) scores], identification threshold [(2.48±0.68) scores]compared with control group [(1.24±0.89) scores and (2.00±0.71) scores, P< 0.05]. The thres holds of detectability and identification threshold were related to MMSE in AD group (r =-0.50,-0.54, P< 0.01). Conclusion The early diagnostic value of olfactory function measurement to AD is very great.
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BACKGROUND: Visual-motor integration (VMI) test was introduced into China in the 1970s and 1990s and widely used for evaluation and identification of problems in intellectual development and learning ability in children due to its good applicability without limitations by language and cultural background.OBJECTIVE: To assess the value of developmental test of VMI in children with hearing handicap, and evaluate its practical feasibility in largescale screening of intelligence problems in these children by comparing its reliability and validity with the norms of children in Shaanxi Province and the USA.DESIGN: A controlled correlation and multiple stepwise regression analysis with randomized cluster sampling.SETTING: Neurological Department of the First Hospital Affiliated to Medical College of Xi' an Jiaotong University.PARTICIPANTS: From January 1998 to December 2000, 638 children under 18 years of age with hearing handicaps were chosen from 6 schools of deaf-mutes in Xi'an City, Xianyang City, Chang'an County, Huxian County,and Lintong County in Shaanxi Province. Another 43 children with hearing handicap including 23 male and 20 female children aged (11.62±1.98) years were selected randomly for EEG and brain electrical activity mapping (BEAM) examination, who had a mean development quotient of VMI of 86.60±15.68. The children were divided by the development quotient into two groups, namely those with development quotient ＜ 86.6 (n=20) and those with development quotient ≥ 86.6 (n=23). METHODS: ① The VMI test was performed in accordance with the Fourth edition of VMI Manual by Beery K.E. The test was terminated when the testee failed to correctly copy three consecutive geometrical figures without time limit. The scale score varied from 0 to 27. ② The reliability test included split-half reliability test in which the items were split into two parts according to odd-even number, re-test reliability that tested the same group of children again in two months and inter-examiner reliability in which two examiners were asked to grade the same test paper.③ The validity test included structural and correlation validity test. Three well-revised and already established norms of scales in China, including Hiskey- Nebraska test of learning aptitude (H-NTLA), performance scale of Wechsler intelligent scale for children (PS-WISC) and Combined Raven's test (CRT), have been chosen as the structure validity criteria. The performance IQ of PS-WISC, learning quotient of H-NTLA, percentile rank of CRT and standard score of VMI were taken respectively for each test in this study.Academic achievements and teachers' and parent's rating were used as the validity correlation criteria. During the administration procedure, a card describing the requirements in detail were presented to the deaf children with reading capacity, while for those too young to read, the teacher was asked to help translate the requirements using standard sign language, but no any hints or clues in relation with the test contents were given. ④ The test did not start until the subjects fully understood the requirement (7314/F/W DYD-300A).EEG recording was performed with the leads deposited according to the international standard 10/20 lead system. Routine EEG had been recorded at least 30 minutes for visual assessment, and stable and representative waves for 120 seconds free of biases or inferences were recorded using unipolar lead from the subjects at rest with the eyes closed and stored in computer.Experienced EEG experts were asked to select the most representative waves of 20 seconds in a double-blind manner to compute the absolute power spectrum of the brain wave.MAIN OUTCOME MEASURES: Reliability and validity of VMI test,relationship between VMI ability and cerebral electrophysiological changes.RESULTS: Totally 638 children under 18 years old with hearing handicap were involved, of whom 72 were eliminated because of lack of data, congenital disease or central nervous system diseases. Finally 566 cases were available for analysis, including 346 male and 220 female children with an average age of (12±3) years. ① The reliability of VMI reached an average of 0.92, varying from 0.63 to 0.99 in each group. The equivalent age corresponding to the scores of the VMI test norm established for the 566 healthy deaf children was lower by an average of (1.79±0.9) years than the equivalent age in the norms of the normal children in Shaanxi Province delayed and USA. ② The standard score of VMI test showed the highest correlation coefficient of 0.661 0 with the learning quotient of H-NTLA, while the correlation with PS-WISC and CRT were 0.357 6 and 0.517 4, respectively.③ Children with higher VMI score showed more powerful absolute spectrum among frequency rangesδ,θ,αl and total power spectrum in the central, parietal and occipital regions of the left hemisphere, respectively.CONCLUSION: VMI test can efficiently reflect the development status of visual-motor integration or intelligence of the school-age deaf children and represent the level of central EEG activity.
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Objective: To find out who is more suitable to be screened by MMSE (mini-mental state examination) Method: A total of 4921 persons aged 55 or above were collected by stratification cluster sampling for urban and rural areas of Xi'an They were screened by MMSE According to different age and education levels, the tenth percentage, median, skewness and kurtosis, and the positive predict value were calculated Results: MMSE scores showed a negative and cliff distributions whether among groups of different education level, among different age groups or in the total sample Moreover, these features was more obvious in relatively younger people (less than 70 years) with higher education level (high school or college), while in those aged more than 70 years with poor education (primary school or illiterate), the distribution of MMSE score was close to normal Consequently, the rates screened out by MMSE was higher in older and poor educated people than in those younger with higher education Multiple regression showed that education level, age, sex, lose of hearing, activity in daily life were factors having influence on score of MMSE Conclusion: In screening dementia, MMSE is more suitable for poor educated older people (older than 70)