Effect of electroacupuncture on regional homogeneity of brain function in rats with vascular cognitive impairment / 中国康复理论与实践

@#Objective To observe the effect of electroacupuncture at Baihui (DU20) and Shenting (DU24) on brain functional activity and working memory of rats with vascular cognitive impairment (VCI). Methods Eighteen Sprague-Dawley rats were included, in which twelve rats were ligated bilateral common carotid arteries and six rats were not ligated (sham group). The modeled rats were randomly divided into model group (n = 6) and electroacupuncture group (n = 6). The electroacupuncture group received electroacupuncture at Baihui and Shenting for four weeks. They were assessed with Y maze and Morris water maze before and after intervention, and scaned with resting-state functional magnetic resonance imaging after intervention to calculate regional homogeneity (ReHo). Results Compared with the sham group, alternation rate of Y maze decreased (P < 0.001), and escape latency of Morris water maze increased (P < 0.05) in the model group and the electroacupuncture group before intervention. Compared with the model group, alternation rate of Y maze increased (P < 0.05), and escape latency of Morris water maze decreased (P < 0.05) after intervention in the electroacupuncture group. Compared with the sham group, ReHo of bilateral hippocampus, olfactory cortex, sensory cortex and auditory cortex, and left striatum decreased in the model group; compared with the model group, ReHo of bilateral prefrontal lobe, hippocampus and olfactory cortex, and left amygdala increased in the electroacupuncture group. Conclusion Electroacupuncture at Baihui and Shenting can improve the memory function of VCI rats, which may be related to the functional activities of prefrontal lobes, hippocampus and amygdala.

Influence of specifically knocking out AMP-activated protein kinase α1 subunit gene in excitatory neurons in brain energy metabolism and cognitive function in mice / 中华神经医学杂志

Objective:To investigate the changes of brain energy metabolism and cognitive function in mice with specifically knocking out AMP-activated protein kinase α1 subunit ( AMPKα1) gene in the excitatory neurons by Cre-loxP recombination system. Methods:Sixteen 6-month-old mice with genotype AMPKα1 flox/flox/Camk2a-Cre/ERT2 obtained by hybrid breeding were randomly divided into AMPKα1 knockout group ( n=8) and AMPKα1 wild-type group ( n=8). Mice in the AMPKα1 knockout group were intraperitoneally injected 0.1 mL tamoxifen (20 mg/mL, dissolved in corn oil) daily for a consecutive 5 d to control AMPKα1 gene knockout in the excitatory neurons; and mice in the AMPKα1 wild-type group were intraperitoneally injected 0.1 mL corn oil daily for a consecutive 5 d. Seven d after that, Morris water maze and T maze experiments were employed to detect the spatial learning and memory abilities and spatial working memory of these mice; chemical exchange saturation transfer imaging (CEST) was used to observe the glucose metabolism in the hippocampus and cortex surrounding the hippocampus; Western blotting was used to detect the AMPKα1 and glutamate receptor 1 (GluR1) protein expressions in the hippocampus and cortex surrounding hippocampus of two groups. Results:(1) Morris water maze showed that, as compared with those in the AMPKα1 wild-type group, mice in the AMPKα1 knockout group had significantly prolonged escape latency ([13.90±3.72] s vs. [22.40±6.28] s; [11.95±3.86] s vs. [22.39±9.77] s]) on the 3 rd and 4 th d of experiment, statistically decreased times crossing the platform ([5.25±1.83] times vs. [1.75±1.28] times, P<0.05). (2) T-maze experiment showed that as compared with that of the AMPKα1 wild-type group, the free alternation rate in mice of the AMPKα1 knockout group was significantly decreased ([73.21±9.16]% vs. [48.21±11.29]%, P<0.05). (3) CEST showed that the glucose metabolism levels in the hippocampus and cortex surrounding the hippocampus of AMPKα1 knockout group were significantly lower than those in AMPKα1 wild-type group (1.51±0.81 vs. 2.77±0.67; 1.31±0.83 vs. 2.42±0.95, P<0.05). (4) Western blotting showed that the AMPKα1 and GluR1 protein expressions in the hippocampus and cortex surrounding the hippocampus of the AMPKα1 wild-type group were significantly higher than those of the AMPKα1 knockout group (AMPKα1: 0.70±0.05 vs. 0.49±0.03, 0.98±0.04 vs. 0.64±0.06; GluR1: 1.22±0.18 vs. 0.60±0.11, 0.96±0.08 vs. 0.79±0.04, P<0.05). Conclusion:Specifically knocking out AMPKα1 in excitatory neurons can result in abnormal glucose metabolism in the brain of mice, and thus cause cognitive dysfunction, whose mechanism may be related to excitatory synaptic disorder caused by energy metabolism disorder.

Cognitive function changes of apolipoprotein E -/- mice after transient global cerebral ischemia by diffusion tensor imaging and magnetic resonance spectroscopy / 中华神经医学杂志

Objective:To investigate the mechanism of learning and memory impairment of apolipoprotein E -/- ( ApoE-/-) mice after transient global cerebral ischemia by diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS). Methods:Ten-week-old C57BL/6(WT) mice and ApoE-/- mice were randomly divided into WT sham-operated group ( n=8), WT 7 d group ( n=12) and WT 30 d group ( n=12), and ApoE-/- sham-operated ( n=8), ApoE-/- 7 d group ( n=12) and ApoE-/- 30 d group ( n=12). The mice in the WT 7 d group, WT 30 d group, ApoE-/- 7 d group, and ApoE-/- 30 d group received bilateral common carotid artery ischemia-reperfusion injury, while mice in the WT sham-operated group and ApoE sham-operated group only stripped the blood vessels without ligation. On the 7 th and 30 th d of modeling, Morrris water maze test was employed to detect the learning and memory abilities of these mice; DTI was used to detect the fractional anisotropy (FA) values in the bilateral hippocampus of mice, and MRS was used to detect the contents of choline complex (Cho) and N-acetylaspartate (NAA) in the bilateral hippocampus of mice. Results:(1) On 2 nd, 3 rd, and 4 th d of water maze experiment, the escape latency of mice in ApoE-/- 7 d group was significantly prolonged as compared with that in the ApoE-/- sham-operated group and WT 7 d group ( P<0.05); since the 3 rd d of water maze experiment, the escape latency of mice in ApoE-/- 30 d group was significantly prolonged as compared with that in WT 30 d group ( P<0.05). The number of times crossing platform in ApoE-/- 7 d group was significantly smaller than that in WT 7 d group, and the residence time in the third quadrant was significantly shorter ( P<0.05); the number of times crossing platform in ApoE-/- 30 d group were significantly smaller as compared with that in the WT 30 d group, and the residence time in the third quadrant was significantly shortened ( P<0.05). (2) DTI results showed that there was no significant difference in bilateral hippocampal FA values between ApoE-/- 7 d group and WT 7 d group ( P>0.05); the bilateral hippocampal FA values of mice in the ApoE-/- 30 d group were statistically lower than those in WT 30 d group ( P<0.05). (3) MRS results showed that the relative contents of hippocampal Cho and NAA in the ApoE-/- 7 d group were significantly lower than those in the WT 7 d group, and the relative contents of hippocampal Cho and NAA in the ApoE-/- 30 d group were significantly lower than those in the WT 30 d group ( P<0.05). Conclusion:ApoE-/- mice have poor learning and memory abilities after transient global cerebral ischemic injury, whose mechanism is closely related to the damage of hippocampal white matter fibers and abnormal metabolism of nerve cells.

Role of glucose Warburg effect in Alzheimer's disease and targeted therapy of AMP-activated protein kinase / 中华神经医学杂志

Brain glucose metabolism disorder is one of the pathophysiological features of Alzheimer's disease (AD), in which aerobic glycolysis (Warburg effect) metabolic pathway abnormality is one of the causes of early cognitive impairment in AD, and improving brain energy metabolism has become an important strategy to prevent AD. AMP-activated protein kinase (AMPK) is a central hub regulating glucose metabolism, the most sensitive molecular compound for sensing fluctuations of energy levels in the body. Activation of AMPK can affect the Warburg effect and its key rate-limiting enzyme activity, regulate brain glucose metabolism involved in the pathogenesis of AD, to achieve the purpose of delaying AD progression and improving cognitive function in early clinical stage. In this review, we will discuss the pathogenesis of AD and targeting of AMPK from the perspective of Warburg effect in glucose metabolism.

Imaging changes in brain microstructural in long-term abstinent from methamphetamine-dependence / 中南大学学报(医学版)

To explore the mechanism for changes in brain microstructure in long-term abstinent from methamphetamine-dependence by using the diffusion tensor imaging (DTI).
 Methods: A total of 26 patients with long-term abstinent methamphetamine-dependence, whose abstinence time more than 14 months, and 26 normal controls all underwent cognitive executive function tests and DTI scans. We used voxel-based analysis to compare the fractional anisotropy (FA) and mean diffusivity (MD) to obtain the abnormal brain regions of DTI parameters between the two groups. Spearman correlation analysis was used to explore the correlation between FA, MD of the brain regions with abnormal parameters and cognitive executive function tests.
 Results: There were no statistical differences in the cognitive executive function tests between the two groups (P>0.05). Compared with the normal control group, the long-term abstinent from methamphetamine-dependence group showed the decreased FA in the right precuneus, right superior frontal gyrus, right calcarine, left inferior temporal gyrus and the increased MD in the right triangular part of inferior frontal gyrus, right precuneus, right posterior cingulate, right middle temporal gyrus, bilateral middle occipital gyrus, left superior parietal lobule, and lobule VIII of cerebellar hemisphere. The MD values of the right middle temporal gyrus in the long-term abstinent group were negatively correlated with the number of completions within 60 seconds (r=-0.504) and within 120 seconds (r=-0.464) .
 Conclusion: The DTI parameters in multiple brain regions from the methamphetamine-dependence patients are still abnormal after a long-term abstinence. DTI can provide imaging evidence for brain microstructural abnormalities in long-term abstinent from methamphetamine-dependence.

Abnormal Metabolic Connectivity in Rats at the Acute Stage of Ischemic Stroke / 神经科学通报·英文版

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.

Correlation of serum level of TNF-α and TGF-β1 with infiltration degree of lymphocytes in labial glands and interstitial lung disease in patients with primary Sjogren's syndrome / 重庆医学

Objective To investigate the correlation between peripheral serum TNF-α and TGF-β1 expression levels with the infiltration degree of lymphocytes in labial glands and interstitial lung disease(ILD) in the patients with primary Sjogren's syndrome (pSS).Methods Serum level of TNF-α and TGF-β1 in 116 patients with pSS and 20 persons undergoing physical examination were measured by ELISA.Meanwhile the labial gland samples in pSS patients were performed the pathological examination.The patients were grouped according to the lesion stage of ILD and pathology grade of labial glands.The serum TNF-α and TGF-β1 levels were statistically analyzed.Results Serum levels of TNF-α and TGF-β1 in the pSS-ILD group were significantly higher than those in the simple pSS group and control group(P＜0.01).The levels of serum TNF-α and TGF-β1 in the simple pSS group were significantly higher than those in the control group(P＜0.01).The levels of serum TNF-α and TGF-β1 in the labial glands lymphocytes infiltration group were significantly higher than those in the labial glands lymphocytes non-infiltration group and control group(P＜0.01),while the levels of serum TNF-α and TGF-β1 in the labial glands lymphocytes non-infiltration group were significantly higher than those in the control group(P＜0.01).The TNF-α and TGF-β1 expression was positively correlated with lymphocytes infiltration lesion grade(r=0.867,0.613,P=0.000);the expression of TNF-α and TGF-β1 was positively correlated with the lesion grade of ILD(r=0.814,0.864,P =0.000);the level of TNF-α was positively correlated with the TGF-β1 relative expression amount(r=0.857,P=0.000).Conclusion TNF-α and TGF-β1 are involved in the lymphocytes infiltration of labial glands and ILD occurrence and develvp ment,and their expression increase may be the cause of labial glands structure destruction and complicating ILD.

An Automatic Method for Generating an Unbiased Intensity Normalizing Factor in Positron Emission Tomography Image Analysis After Stroke / 神经科学通报·英文版

Positron emission tomography (PET) imaging of functional metabolism has been widely used to investigate functional recovery and to evaluate therapeutic efficacy after stroke. The voxel intensity of a PET image is the most important indicator of cellular activity, but is affected by other factors such as the basal metabolic ratio of each subject. In order to locate dysfunctional regions accurately, intensity normalization by a scale factor is a prerequisite in the data analysis, for which the global mean value is most widely used. However, this is unsuitable for stroke studies. Alternatively, a specified scale factor calculated from a reference region is also used, comprising neither hyper- nor hypo-metabolic voxels. But there is no such recognized reference region for stroke studies. Therefore, we proposed a totally data-driven automatic method for unbiased scale factor generation. This factor was generated iteratively until the residual deviation of two adjacent scale factors was reduced by < 5%. Moreover, both simulated and real stroke data were used for evaluation, and these suggested that our proposed unbiased scale factor has better sensitivity and accuracy for stroke studies.

Effects of Electroacupuncture on Nerve Bundle of Motor Cortex and Striatum in Rats with Ischemic Stroke:Observed with Diffusion Tensor Imaging / 中国康复理论与实践

@#Objective To explore the effect of electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on motor behaviors, the axonal integrity and nerve bundle of motor cortex and striatum in rat model of ischemic stroke induced by middle cerebral artery occlusion (MCAO) using diffusion tensor imaging (DTI). Methods Thirty-six adult male Sprague-Dawley rats were randomly assigned to sham opera-tion group (sham group), ischemia control group (model group) and electroacupuncture treatment group (EA group) with twelve rats in each group. The later two groups were occluded their middle cerebral arteries for two hours. Twenty-four hours after modeling, EA group re-ceived electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on the paralyzed limb, once a day, for 14 days. They were assessed with modified Neurological Severity Scores (mNSS) and Rota-rod test, and scanned with small animal magnetic resonance imaging system for T2-weighted image (T2WI) and DTI, the infarct size, related fractional anisotropy (rFA) and related number of tracks of motor cortex and striatum were recorded. Results Compared with the sham group, the score of mNSS increased in the model group and EA group after model-ing, and was lower in EA group than in the model group seven days and 14 days after intervention (P<0.05). Rota-rod test showed that the retention time was significantly longer in EA group than in the model group (P<0.05). T2WI showed that the infarct size was smaller in EA group than in the model group (P<0.05). DTI showed that rFA in motor cortex and striatum was higher in EA group than in the model group (P<0.05), as well as the related number of tracks (P<0.05) in motor cortex. Conclusion Electroacupuncture at Quchi and Zusanli acupoints could improve the motor function in rats with ischemic stroke, which may be related to the recovery of nerve bundle of motor cortex and stri-atum in ischemic side.

Research on the reform of curriculum system of health service management / 中华医学教育探索杂志

Objective To understand the needs to reform curriculum for the graduate students in health management, and to provide evidence for the reform of the curriculum system. Methods From Jan-uary 2015 to May from China's colleges and universities carrying out health management professional post-graduate education, graduate students and supervisors from 3 universities were selected, and self-designed questionnaires were used to investigate their views on training objectives, abilities and curriculum settings, as well as the needs and suggestions for curriculum reform. The questionnaire survey data were collected and analyzed by SPSS 17.0. Results 120 questionnaires were issued and 100 were recovered in the study, with a recovery rate of 83.3％. 84.0％ of the graduate students did not manage relevant work experience before entering the school. The graduate students thought that we should focus on the research and teaching ability training related to the management of health services, and then the cultivation of management ability. There were 60 questionnaires for instructors, and 51 were recovered, with a recovery rate of 85.0％. With regard to the demand for ability training , teachers and graduate students tended to agree on the goal and focus of the training. 100.0％instructors believed that learning was an important course, only 11.2％ of the students thought that the course of study was not important, but to the current status of health manage-ment professional postgraduate courses, 79.3％ instructors believed that the current curriculum was reasonable, and only 53.5％of the students thought it reasonable. Conclusion The emphasis should be given to optimizing the course setting, adding practical and innovative courses, and strengthening the training of scientific research, etc., which is the only way to improve the quality of health management postgraduate education and meet the needs of health development.

Learning and Memory Deficit and Demyelination of Corpus Callosum in APP/PS1 Transgenic Mice / 中国康复理论与实践

Objective To investigate the relationship between learning and memory deficit and demyelination of the corpus callosum in twelve-month old APP/PS1 transgenic mice. Methods Twelve twelve-month old APP/PS1 transgenic mice were as AD group, and age-matched wild type (WT) littermates were as WT group. Learning and memory ability was tested with Morris water maze, and the mor-phology of nerve fiber of corpus callosum was detected with Luxol Fast Blue staining. Immunohistochemistry was used to detect myelin ba-sic protein (MBP) in the corpus callosum. Thioflavine S staining was used to detect amyloid plaque in the corpus callosum. Results Com-pared with WT group, the latency increased (Z>2.873, P<0.01) and the times crossing the location of the platform decreased (t=-7.339, P<0.001) in AD group. The nerve fibers were sparse and disorganized, with a lot of vacuoles in the corpus callosum of AD group. The positive expression of MBP in the corpus callosum was significantly decreased (t=-4.481, P<0.001) in AD group compared with WT group. There were amyloid plaques in the corpus callosum of AD group. Conclusion Twelve-month old APP/PS1 transgenic mice exhibit learning and memory deficit, which may be attributed to the deposition of the amyloid plaque mediated demyelinated injury of the corpus callosum.

A correlation study on depression and life events of patients with primary sjogren syndrome / 中华行为医学与脑科学杂志

Objective To explore the relationship between life events and depression of patients with primary sjgren's syndrome (PSS).Methods 80 patients with PSS complicating depressive disorder were tested by self-rating depression scale(SDS) and life event scale (LES),and compared with the control group including 80 PSS patients with non-depressive disorder matched with age and sex.Then the correlation between SDS and LES were analyzed.Results The total score of life events (32.72 ± 13.93),the score of negative life events (24.36 ±11.24),the score of SDS(58.60 ± 16.78) and the frequency of life events(91.3％) in the research group were higher than those in control group(P ＜ 0.05),but the positive life events score (7.15 ± 5.84) was lower than that in control group (9.76 ± 7.29),and there was statistically significant difference between the two groups (P ＜ 0.05),there were more negative life events,especially on the aspects of family,work and study in the research group.There was positive correlation among the negative life events score,total score of life events and SDS score in the research group(P＜ 0.01),meanwhile,negative correlation was revealed between the score of positive life events and SDS score in the research group(P ＜ 0.05).Conclusion Patients with PSS complicating depressive disorder experienced more negative life events which play an important role in depression of patients with PSS.