Causal influences of salience/cerebellar networks on dorsal attention network subserved age-related cognitive slowing.

Age-related cognitive slowing is a prominent precursor of cognitive decline. Functional neuroimaging studies found that cognitive processing speed is associated with activation and coupling among frontal, parietal and cerebellar brain networks. However, how the reciprocal influences of inter- and intra-network coupling mediate age-related decline in processing speed remains insufficiently studied. This study examined how inter- and intra-brain network influences mediate age-related slowing. We were interested in the fronto-insular salience network (SN), frontoparietal dorsal attention network (DAN), cerebellar network (CN) and default mode network (DMN). Reaction time (RT) and functional MRI data from 84 participants (aged 18-75) were collected while they were performing the Arrow Task in visual or audial forms. At the subject level, effective connectivities (ECs) were estimated with regression dynamic causal modelling. At the group level, structural equation models (SEMs) were used to model latent speed based on age and the EC mediators. Age was associated with decreased speed and increased inter-network effective connectivity. The CN exerting influence on the DAN (CN → DAN EC) mediated, while the SN → DAN EC suppressed age-related slowing. The DMN and intra-network ECs did not seem to play significant roles in slowing due to ageing. Inter-network connectivity from the CN and SN to the DAN contributes to age-related slowing. The seemingly antagonizing influences of the CN and SN indicate that increased task-related automaticity and decreased effortful control on top-down attention would promote greater speed in older individuals.

Emerging blood exosome-based biomarkers for preclinical and clinical Alzheimer's disease: a meta-analysis and systematic review.

Blood exosomes, which are extracellular vesicles secreted by living cells into the circulating blood, are regarded as a relatively noninvasive novel tool for monitoring brain physiology and disease states. An increasing number of blood cargo-loaded exosomes are emerging as potential biomarkers for preclinical and clinical Alzheimer's disease. Therefore, we conducted a meta-analysis and systematic review of molecular biomarkers derived from blood exosomes to comprehensively analyze their diagnostic performance in preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease. We performed a literature search in PubMed, Web of Science, Embase, and Cochrane Library from their inception to August 15, 2020. The research subjects mainly included Alzheimer's disease, mild cognitive impairment, and preclinical Alzheimer's disease. We identified 34 observational studies, of which 15 were included in the quantitative analysis (Newcastle-Ottawa Scale score 5.87 points) and 19 were used in the qualitative analysis. The meta-analysis results showed that core biomarkers including Aß1-42, P-T181-tau, P-S396-tau, and T-tau were increased in blood neuron-derived exosomes of preclinical Alzheimer's disease, mild cognitive impairment, and Alzheimer's disease patients. Molecules related to additional risk factors that are involved in neuroinflammation (C1q), metabolism disorder (P-S312-IRS-1), neurotrophic deficiency (HGF), vascular injury (VEGF-D), and autophagy-lysosomal system dysfunction (cathepsin D) were also increased. At the gene level, the differential expression of transcription-related factors (REST) and microRNAs (miR-132) also affects RNA splicing, transport, and translation. These pathological changes contribute to neural loss and synaptic dysfunction. The data confirm that the above-mentioned core molecules and additional risk-related factors in blood exosomes can serve as candidate biomarkers for preclinical and clinical Alzheimer's disease. These findings support further development of exosome biomarkers for a clinical blood test for Alzheimer's disease. This meta-analysis was registered at the International Prospective Register of Systematic Reviews (Registration No. CRD4200173498, 28/04/2020).

The Global Burden of Disease attributable to low physical activity and its trends from 1990 to 2019: An analysis of the Global Burden of Disease study.

Introduction: Low physical activity (LPA) is associated with several major non-communicable diseases (NCDs) and premature mortality. In this study, we aimed to assess the global burden and trends in disease attributable to LPA (DALPA) from 1990 to 2019. Methods: Annual age-standardized disability-adjusted life years (DALYs) and death rates of DALPA [all-cause and five specific causes (ischaemic heart disease, diabetes mellitus, stroke, colon and rectal cancer, and breast cancer)] by sex, age, geographical region and social deprivation index (SDI) score from 1990 to 2019 were available from the Global Burden of Disease (GBD) study 2019. The estimated annual percentage changes (EAPCs) were calculated to quantify the changing trend. A generalized linear model (GLM) was used to explore the relationship between DALYs/death rates of DALPA and sociodemographic factors. Results: Globally, in 2019, the age-standardized DALYs and death rates of DALPA were 198.42/100,000 (95% UI: 108.16/100,000-360.32/100,000) and 11.10/100,000 (95% UI: 5.66/100,000-19.51/100,000), respectively. There were 15.74 million (8.51-28.61) DALYs and 0.83 million (0.43-1.47) deaths attributable to LPA. Overall, age-standardized DALYs and death rates presented significant downward trends with EAPCs [-0.68% (95% CI: -0.85- -0.50%) for DALYs and -1.00% (95% CI: -1.13- -0.86%) for deaths] from 1990 to 2019. However, age-standardized DALYs and death rates of diabetes mellitus attributable to LPA were substantially increased [EAPC: 0.76% (95% CI: 0.70-0.82%) for DALYs and 0.33% (95% CI: 0.21-0.51%) for deaths]. In the 15-49 age group, DALPA presented significant upward trends [EAPC: 0.74% (95% CI: 0.58-0.91%) for DALYs and 0.31% (95% CI: 0.1-0.51%) for deaths]. The GLM revealed that higher gross domestic product and current health expenditure (% of GDP) were negatively associated with DALYs and death rates of DALPA. Conclusion: Although global age-standardized DALYs and death rates of DALPA presented downward trends, they still cause a heavy burden worldwide. These rates showed upward trends in the diabetic and 15-49 age groups, which need more attention and health interventions.

Subsequent Acupuncture Reverses the Aftereffects of Intermittent Theta-Burst Stimulation.

Objective: This study explored whether acupuncture affects the maintenance of long-term potentiation (LTP)-like plasticity induced by transcranial magnetic stimulation (TMS) and the acquisition of motor skills following repetitive sequential visual isometric pinch task (SVIPT) training. Methods: Thirty-six participants were recruited. The changes in the aftereffects induced by intermittent theta-burst stimulation (iTBS) and followed acupuncture were tested by the amplitude motor evoked potential (MEP) at pre-and-post-iTBS for 30 min and at acupuncture-in and -off for 30 min. Secondly, the effects of acupuncture on SVIPT movement in inducing error rate and learning skill index were tested. Results: Following one session of iTBS, the MEP amplitude was increased and maintained at a high level for 30 min. The facilitation of MEP was gradually decreased to the baseline level during acupuncture-in and did not return to a high level after needle extraction. The SVIPT-acupuncture group had a lower learning skill index than those in the SVIPT group, indicating that acupuncture intervention after SVIPT training may restrain the acquisition ability of one's learning skills. Conclusion: Acupuncture could reverse the LTP-like plasticity of the contralateral motor cortex induced by iTBS. Subsequent acupuncture may negatively affect the efficacy of the acquisition of learned skills in repetitive exercise training.

The Effects of Exercise Interventions on Balance Capacity in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

The effect of exercise intervention on balance capacity among type 2 diabetes mellitus (T2DM) patients has not been evaluated. The objective of this systematic review and meta-analysis is to investigate the effect of exercise intervention on balance capacity among T2DM patients compared to the control group (usual care, waitlist, no-treatment, education). We conducted a comprehensive literature search through PubMed, EMBASE, Physiotherapy Evidence Database (PEDro), Cochrane library, Web of Science (WOS) from inception to August 2020. The literature language was limited to English. Randomized controlled trials (RCTs) or quasi-experimental (Q-E) trials that examined the effect of exercise intervention on balance capacity among T2DM patients were included. We used the standard methods of meta-analysis to evaluate the outcomes of exercise intervention for balance capacity of T2DM patients. A total of 14 trials (11 RCTs and 3 Q-E trials) involving 883 participants were eligible. The meta-analysis of some studies demonstrated that exercise intervention could significantly improve Berg Balance Scale (BBS) (MD = 2.56; 95%CI [0.35, 4.77]; P = .02), SLST (Single Leg Stance Test) under the eyes-open (EO) condition (MD = 3.63; 95%CI [1.79, 5.47]; P = .0001) and eyes-close (EC) condition (MD = 0.41; 95%CI [0.10, 0.72]; P = .01) compared to control group. There was no significant difference in Time Up and Go Test (TUGT) (MD = -0.75; 95%CI [-1.69, 0.19]; P = .12) and fall efficacy (SMD = -0.44; 95%CI [-0.86, -0.01]; P = .05). Narrative review of some studies indicated that exercise intervention could improve postural stability measured by Sensory Organization Test (SOT) and Center of Pressure (COP) variables, etc. This systematic review and meta-analysis summarized that exercise intervention could improve balance capacity in T2DM patients. However, further studies with high quality are required to evaluate its effect.

Common and distinct neural trends of allocentric and egocentric spatial coding: An ALE meta-analysis.

The uniqueness of neural processes between allocentric and egocentric spatial coding has been controversial. The distinctive paradigms used in previous studies for manipulating spatial coding could have attributed for the inconsistent results. This study was aimed to generate converging evidence from previous functional brain imaging experiments for collating neural substrates associated with these two types of spatial coding. An additional aim was to test whether test-taking processes would have influenced the results. We obtained coordinate-based functional neuroimaging data for 447 subjects and performed activation likelihood estimation (ALE) meta-analysis. Among the 28 experiments, the results indicate two common clusters of convergence. They were the right precuneus and the right superior frontal gyrus as parts of the parieto-frontal circuit. Between-type differences were in the parieto-occipital circuit, with allocentric showing convergence in the superior occipital gyrus (SOG) cluster compared with egocentric showing convergence in the middle occipital gyrus (MOG) cluster. Task-specific influences were only found in allocentric spatial coding. Spatial judgment-oriented tasks seem to increase the demands on manipulating spatial relationships among the visual objects, while spatial navigation tasks seem to increase the demands on maintaining object representations. Our findings address the theoretical controversies on spatial coding that both the allocentric and egocentric types are common in their processes mediated by the parieto-frontal network, while unique and additional processes in the allocentric type are mediated by the parieto-occipital network. The positive results on possible task-specific confound offer insights into the future design of spatial tasks for eliciting spatial coding processes.

Ferulic Acid Ameliorates Alzheimer's Disease-like Pathology and Repairs Cognitive Decline by Preventing Capillary Hypofunction in APP/PS1 Mice.

Brain capillaries are crucial for cognitive functions by supplying oxygen and other nutrients to and removing metabolic wastes from the brain. Recent studies have demonstrated that constriction of brain capillaries is triggered by beta-amyloid (Aß) oligomers via endothelin-1 (ET1)-mediated action on the ET1 receptor A (ETRA), potentially exacerbating Aß plaque deposition, the primary pathophysiology of Alzheimer's disease (AD). However, direct evidence is still lacking whether changes in brain capillaries are causally involved in the pathophysiology of AD. Using APP/PS1 mouse model of AD (AD mice) relative to age-matched negative littermates, we identified that reductions of density and diameter of hippocampal capillaries occurred from 4 to 7 months old while Aß plaque deposition and spatial memory deficit developed at 7 months old. Notably, the injection of ET1 into the hippocampus induced early Aß plaque deposition at 5 months old in AD mice. Conversely, treatment of ferulic acid against the ETRA to counteract the ET1-mediated vasoconstriction for 30 days prevented reductions of density and diameter of hippocampal capillaries as well as ameliorated Aß plaque deposition and spatial memory deficit at 7 months old in AD mice. Thus, these data suggest that reductions of density and diameter of hippocampal capillaries are crucial for initiating Aß plaque deposition and spatial memory deficit at the early stages, implicating the development of new therapies for halting or curing memory decline in AD.

Cortical Hemodynamic Response Associated with Spatial Coding: A Near-Infrared Spectroscopy Study.

Allocentric and egocentric are two types of spatial coding. Previous studies reported the dorsal attention network's involvement in both types. To eliminate possible paradigm-specific confounds in the results, this study employed fine-grained cue-to-target paradigm to dissociate allocentric (aSC) and egocentric (eSC) spatial coding. Twenty-two participants completed a custom visuospatial task, and changes in the concentration of oxygenated hemoglobin (O2-Hb) were recorded using functional near-infrared spectroscopy (fNIRS). The least absolute shrinkage and selection operator-regularized principal component (LASSO-RPC) algorithm was used to identify cortical sites that predicted the aSC and eSC conditions' reaction times. Significant changes in O2-Hb concentration in the right inferior parietal lobule (IPL) and post-central gyrus regions were common in both aSC and eSC. Results of inter-channel correlations further substantiate cortical activities in both conditions were predominantly over the right parieto-frontal areas. Together with right superior frontal gyrus areas be the reaction time neural correlates, the results suggest top-down attention and response-mapping processes are common to both spatial coding types. Changes unique to aSC were in clusters over the right intraparietal sulcus, right temporo-parietal junction, and left IPL. With the left pre-central gyrus region, be the reaction time neural correlate, aSC is likely to involve more orienting attention, updating of spatial information, and object-based response selection and inhibition than eSC. Future studies will use other visuospatial task designs for testing the robustness of the findings on spatial coding processes.

Timing of Acupuncture during LTP-Like Plasticity Induced by Paired-Associative Stimulation.

The aim of this study was to investigate the time-dependent effects of acupuncture on the excitability and long-term potentiation- (LTP-) like plasticity induced by paired-associative stimulation (PAS) over the primary motor cortex (M1). The present examination is the first to report the influence of acupuncture on the motor-evoked potential (MEP) throughout the treatment process, including baseline (before acupuncture), the needle in situ, and the needle removal. Subsequently, the LTP-like plasticity induced by paired-associative stimulation (PAS) was explored, which consisted of 200 pairs of electrical stimulation of the ulnar nerve at the first dorsal interosseous (FDI), followed by transcranial magnetic stimulation (TMS) over the bilateral M1. TMS-MEP amplitudes over the bilateral M1 in resting conditions were measured throughout the whole treatment process. Finally, we confirmed the behavioral measurements. Significant changes were found in both the contralateral and ipsilateral acupuncture sizes as compared to the baseline values. Our results indicated that acupuncture modulated the excitability of M1, and the synaptic plasticity was time-dependent. We concluded that acupuncture should be combined with rehabilitation techniques to improve the motor function in stroke patients. Therefore, we put forward the combined application of the acupuncture timing and rehabilitation for higher therapeutic effectiveness. This trial was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR-IPR-1900020515).

Neuroprotective Effects of Salidroside on Cerebral Ischemia/Reperfusion-Induced Behavioral Impairment Involves the Dopaminergic System.

Salidroside, a phenylpropanoid glycoside, is the main bioactive component of Rhodiola rosea L. Salidroside has prominent anti-stroke effects in cerebral ischemia/reperfusion models. However, the underlying mechanisms of its actions are poorly understood. This study examined the anti-stroke effects of salidroside in middle cerebral artery occlusion (MCAO)-induced rat model of stroke and its potential mechanisms involving the dopaminergic system. Salidroside administration increased the levels of dopamine (DA), homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the ipsilateral striatum after induction of transient ischemia, which were assessed using microdialysis with high-performance liquid chromatography coupled with electrochemical detection (HPLC-ECD). Furthermore, treatment with salidroside ameliorated neurobehavioral impairment, assessed with the modified neurological severity scores (mNSS), the balance beam test, and the foot fault test. Moreover, enzyme-linked immunosorbent assay (ELISA) suggested that MCAO-induced reduction in monoamine oxidase (MAO) was inhibited by salidroside. Immunohistochemical and immunofluorescence analyses revealed high level of tyrosine hydroxylase (TH) in the ipsilateral striatal caudate putamen (CPu) after cerebral ischemia/reperfusion, which could be further elevated by salidroside. In addition, salidroside could reverse the decreased immunoreactivity of TH in the substantia nigra pars compacta (SNpc). These results suggest that the anti-stroke effects of salidroside in MCAO-induced cerebral ischemia/reperfusion may involve the modulation of monoamine metabolism in the striatum and SNpc, which may be related to the function of the dopaminergic system in the rat brain.

Effect of Tai Chi on Cardiac and Static Pulmonary Function in Older Community-Dwelling Adults at Risk of Ischemic Stroke: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of tai chi exercise on cardiac and static lung function for older community-dwelling adults at risk of ischemic stroke. METHODS: A total of 170 older community-dwelling adults (aged 55-75 years old) at risk of ischemic stroke were allocated to either tai chi training group (85 cases, five 60-min sessions of tai chi training per week for 12 weeks) or control group (85 cases, usual pbysical activity for 12 weeks) using a computer-generated randomization. The echocardiographic parameters of cardiac structure, cardiac function and static lung function were measured at baseline, after 12 weeks of intervention and additional 12-week follow-up period by a blinded professional staffmember using a color Doppler ultrasound imaging device or a cardiopulmonary function instrument. The t test and linear mixed model based on the intentionto-treat analysis principle was used to calculate the effect. The adverse effect was observed. RESULTS: Most of echocardiographic parameters on the cardiac structure, cardiac function and static lung function between the tai chi group and control group did not have a significant difference either post 12-week intervention or additional 12-week follow-up period. Only three parameters involving in right ventricular diameter (P=0.024), main pulmonary artery diameter (P=0.002) and vital capacity maximum (P=0.036) were beneficial to be improved in the tai chi group compared to the control group by the analysis of mixed linear model. No adverse effects were found during the intervention period. CONCLUSION: The 12-week tai chi exercise did not have an obvious beneficial effect on cardiac structure, cardiac function and static lung function in older community-dwelling adults at risk of ischemic stroke. The study with a longer duration of intervention should be necessary. (Trial registration No. ChiCTR-TRC-13003601).

Effects of core strength training combined with Tai Chi Chuan for the musculoskeletal system and cardiopulmonary function in older adults: A study protocol for a randomized controlled trial.

BACKGROUND: According to the national census, China has gradually become an aging society; moreover, aging has become an irreversible worldwide trend in the twenty-first century. Aging can lead to decreased physical function, mobility, cardiopulmonary function and quality of life (QOL). The feasibility and benefits of core strength training (CST) and Tai Chi Chuan (TCC) in older adults (including improving cardiovascular, musculoskeletal, and mental health outcomes) have been confirmed in previous studies. To date, these exercise programmes have not been systematically compared, and the potential benefits of their combined use have not been tested. The primary objective of this study protocol is to evaluate the effects of CST compared to those of TCC on the function of the musculoskeletal system and the cardiopulmonary system in older adults.The second objective is to test the effectiveness of combined physical training that incorporates CST and TCC. METHODS: A randomized, single-blind, parallel-controlled trial will be conducted. Three hundred eighty-four participants who meet the eligibility criteria will be randomly allocated into a control group, a CST group, a TCC group, and a combined group in a 1:1:1:1 ratio. Participants in the CST group and the TCC group will respectively receive CST and TCC training at a frequency of 1 hour per day, 5 days per week, totally 12 weeks. Participants in the combined group will receive 30 minutes CST and 30 minutes TCC training per day, 5 days per week, totally 12 weeks. No specific exercises will be required of the participants in the control group. Both musculoskeletal and cardiopulmonary function outcomes, including bone density detection, balance and coordination ability, walking ability, pain visual analogue scale (VAS) score, fall risk assessment, activities of daily living, pulmonary function tests, color sonography and electrocardiogram, will be evaluated by blinded operators at baseline, 13 weeks and 25 weeks (follow-up period). DISCUSSION: The results of this study protocol are expected to clarify the synergistic effect of CST and TCC training on musculoskeletal and cardiopulmonary function in older adults. Furthermore, these findings will confirm whether combined or exclusive CST and TCC training, is more effective at improving functional outcomes in the elderly. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-IOR-17010769. Registration date: March 3, 2017.

Gualou Guizhi decoction promotes neurological functional recovery and neurogenesis following focal cerebral ischemia/reperfusion.

Recovery following stroke involves neurogenesis and axonal remodeling within the ischemic brain. Gualou Guizhi decoction (GLGZD) is a Chinese traditional medicine used for the treatment of post-stroke limb spasm. GLGZD has been reported to have neuroprotective effects in cerebral ischemic injury. However, the effects of GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion. Neurological function was assessed immediately after reperfusion using Longa's 5-point scoring system. The rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group were given sham operation. The rats in the GLGZD group were intragastrically administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle and sham groups were intragastrically administered distilled water. Modified neurological severity score test, balance beam test and foot fault test were used to assess motor functional changes. Nissl staining was performed to evaluate histopathological changes in the brain. Immunofluorescence staining was used to examine cell proliferation using the marker 5-bromo-2'-deoxyuridine (BrdU) as well as expression of the neural precursor marker doublecortin (DCX), the astrocyte marker glial fibrillary acidic protein (GFAP) and the axon regeneration marker growth associated protein-43 (GAP-43). GLGZD substantially mitigated pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive cells in the subventricular zone of the ischemic hemisphere, increased GAP-43 expression in the cortical peri-infarct region, and improved motor function. These findings suggest that GLGZD promotes neurological functional recovery by increasing cell proliferation, enhancing axonal regeneration, and increasing the numbers of neuronal precursors and astrocytes in the peri-infarct area.

Psychometric Properties of the Chinese (Putonghua) Version of the Oxford Cognitive Screen (OCS-P) in Subacute Poststroke Patients without Neglect.

BACKGROUND: Oxford Cognitive Screen is designed for assessing cognitive functions of poststroke patients. This study was aimed to assess the psychometric properties of the Chinese (Putonghua) version of the Oxford Cognitive Screen-Putonghua (OCS-P) for use among poststroke patients without neglect. METHODS: Expert review panel evaluated content validity of the Chinese-translated items. After pilot tested the translated items, the patients and healthy participants completed the OCS-P as well as the Montreal Cognitive Assessment (MoCA-ChiB) and Goldenberg's test. A group of patients completed OCS-P for the second time within seven days. Data analyses included confirmatory factor analysis, item difficulty and item-total correlation, inter- and intrarater reliability, internal consistency, and between-group discrimination. RESULTS: One hundred patients and 120 younger (n = 60) or older (n = 60) healthy participants completed all the tests. Modifications were required for items in the "Picture Naming", "Orientation", and "Sentence Reading" subscales. Confirmatory factor analysis revealed a three-factor structure for the OCS-P subscales. The internal consistency coefficients for the three identified test dimensions were 0.30 to 0.52 (Cronbach's alpha). Construct validity coefficients between the OCS-P and MoCA-ChiB subscales were 0.45 < r < 0.79 (p < 0.001) and the "Praxis" subscale of OCS-P and Goldenberg's test was r = 0.72 (p < 0.001). The interrater reliability coefficients for the subscales were in general higher than the intrarater reliability coefficients. The "Picture Naming" and "Numerical Cognition" subscales were the most significant (p = 0.003) for differentiating patient participants from their older healthy counterpart. CONCLUSION: This study generated satisfactory evidence on the content validity, substantive validity, construct validity, inter- and intrarater reliability, and known-group discrimination of the OCS-P. They support its application among poststroke patients who speak Putonghua. Future studies could review the existing five-dimension domains for improving its structural validity and internal consistency as well as generate evidence of the OCS-P for use among the poststroke patients with neglect.

Gualou Guizhi decoction reverses brain damage with cerebral ischemic stroke, multi-component directed multi-target to screen calcium-overload inhibitors using combination of molecular docking and protein-protein docking.

Stroke is a disease of the leading causes of mortality and disability across the world, but the benefits of drugs curative effects look less compelling, intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine compound prescription, it has been used to human clinical therapy of sequela of cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved prescription against intracellular calcium overload could decreased the concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats. GLGZD contains Trichosanthin and various small molecular that they are the potential active ingredients directed against NR2A, NR2B, FKBP12 and Calnodulin target proteins/enzyme have been screened by computer simulation. "Multicomponent systems" is capable to create pharmacological superposition effects. The Chinese medicine compound prescriptions could be considered as promising sources of candidates for discovery new agents.

Neuroprotection of a sesamin derivative, 1, 2-bis [(3-methoxyphenyl) methyl] ethane-1, 2-dicaroxylic acid (MMEDA) against ischemic and hypoxic neuronal injury.

OBJECTIVES: Stroke may cause severe neuronal damage. The sesamin have been demonstrated to possess neuroprotection by its antioxidant and anti-inflammatory properties. One sesamin derivative was artificially composited, 1, 2-bis [(3-methoxyphenyl) methyl] ethane-1, 2-dicaroxylic acid (MMEDA) had been developed to study its antioxidative activity and neuroprotection. MATERIALS AND METHODS: The infaction of Sprague Dawley (SD) rats and hypoxia models of BV-2 microglia or PC12 cells were investigated for in vivo and in vitro test respectively. Lipid peroxidation and reactive oxygen species (ROS), prostaglandin E2 (PGE2) and related signaling pathways from hypoxic cells were analyzed by ELISA or Western blot assay, respectively. RESULTS: MMEDA showed a protective effect when given 90 min after the focal cerebral ischemia. The neuroprotection of MMEDA was further confirmed by attenuating ROS and PGE2 release from hypoxic BV-2 or PC12 cells. MMEDA significantly reduced hypoxia-induced JNK and caspase-3 (survival and apoptotic pathways) in PC12 cells. CONCLUSION: The neuroprotective effect of MMEDA on ischemia/hypoxia models was involved with its antioxidative activity and anti-inflammatory effects. These results suggest that MMEDA exert effective neuroprotection against ischemia/hypoxia injury.

Altered functional connectivity in patients with post-stroke memory impairment: A resting fMRI study.

Post-stroke memory dysfunction (PMD) is one of the most common forms of cognitive impairment among stroke survivors. However, only a limited number of studies have directly investigated the neural mechanisms associated with memory decline. The aim of the present study was to identify dynamic changes in the functional organization of the default mode network (DMN) and the dorsal attention network of patients with PMD. A total of 27 patients with PMD who experienced a stroke in the right hemisphere were enrolled in the current study, along with 27 healthy control subjects matched by age, sex, and educational level. A behavioral examination and functional magnetic resonance imaging scan were performed. The data were analyzed using an independent component analysis method. The results revealed a significantly increased functional connectivity between the DMN and prefrontal cortex (left middle/inferior frontal and left precentral gyri), temporal regions (left superior temporal gyrus), and bilateral and posterior cingulate gyri/precuneus (P<0.001). There was also a significantly decreased functional connectivity between the DMN and right middle temporal gyrus, left uvula, and right inferior parietal lobule, and between the dorsal attention network and prefrontal cortex (left precentral/inferior and right inferior/middle frontal gyri), right inferior parietal gyrus, and right insula (P<0.001). These results suggest that the stroke affected both the lesioned and contralesional hemispheres. The prefrontal cortex, temporal regions, insula, and posterior cingulate gyrus/precuneus serve a crucial role in memory processing.

The effects of aerobic exercise on the structure and function of DMN-related brain regions: a systematic review.

Physical activity may play a role in both the prevention and slowing of brain volume loss and may be beneficial in terms of improving the functional connectivity of brain regions. But much less is known about the potential benefit of aerobic exercise for the structure and function of the default mode network (DMN) brain regions. This systematic review examines the effects of aerobic exercise on the structure and function of DMN brain regions in human adulthood. Seven electronic databases were searched for prospective controlled studies published up to April 2015. The quality of the selected studies was evaluated with the Cochrane Collaboration's tool for assessing the risk of bias. RevMan 5.3 software was applied for data analysis. Finally, 14 studies with 631 participants were identified. Meta-analysis revealed that aerobic exercise could significantly increase right hippocampal volume (SMD = 0.26, 95% CI 0.01-0.51, p = 0.04, I2 = 7%, 4 studies), and trends of similar effects were observed in the total (SMD = 0.12, 95% CI -0.17 to 0.41, p = 0.43, I2 = 0%, 5 studies), left (SMD = 0.12, 95% CI -0.13 to 0.37, p = 0.33, I2 = 14%, 4 studies), left anterior (SMD = 0.12, 95% CI -0.16 to 0.40, p = 0.41, I2 = 74%, 2 studies) and right anterior (SMD = 0.10, 95% CI -0.17 to 0.38, p = 0.46, I2 = 76%, 4 studies) hippocampal volumes compared to the no-exercise interventions. A few studies reported that relative to no-exercise interventions, aerobic exercise could significantly decrease the atrophy of the medial temporal lobe, slow the anterior cingulate cortex (ACC) volume loss, increase functional connectivity within the hippocampus and improve signal activation in the cingulate gyrus and ACC. The current review suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex and the medial temporal areas of the DMN. Moreover, aerobic exercise may increase functional connectivity or activation in the hippocampus, cingulate cortex and parahippocampal gyrus regions of the DMN. However, considering the quantity and limitations of the included studies, the conclusion could not be drawn so far. Additional randomized controlled trials (RCTs) with rigorous designs and longer intervention periods are needed in the future.

Alisol A 24-Acetate, a Triterpenoid Derived from Alisma orientale, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling.

Alisol A 24-acetate, a triterpenoid extracted from Alisma orientale, has shown antiatherosclerotic actions. The purpose of this study was to evaluate the inhibition of alisol A 24-acetate on oxidized low-density lipoprotein (Ox-LDL)-induced phenotypic transformation and migration of rat vascular smooth muscle cells (VSMCs), and to explore the underlying mechanisms. VSMCs were pretreated with alisol A 24-acetate and a specific extracellular signal-regulated kinase (ERK) inhibitor, U0126, and then stimulated with 50 mg/l Ox-LDL in vitro. The expression of VSMC phenotypic marker SM22α was determined using immunocytochemistry, and the migration of VSMCs was detected using a scratch-wound healing assay. The expression of matrix metalloproteinase (MMP)-9, MMP-2, phosphorylated ERK1/2 (pERK1/2) and total ERK was determined. Ox-LDL treatment caused a reduction in SM22α expression, VSMC transformation to the synthetic phenotype, increased MMP-2 and MMP-9 synthesis, the extension of VSMC migration distance and the upregulation of pERK1/2 expression, while the addition of alisol A 24-acetate or U0126 resulted in the elevation of SM22α expression, VSMC transformation to the contractile phenotype, a reduction in MMP-2 and MMP-9 expression, the shortening of cell migration distance and decreased pERK1/2 expression. The results of this study demonstrate that alisol A 24-acetate effectively reverses the phenotypic transformation and inhibits the migration of VSMCs, which may be associated with the suppression of the ERK1/2 signaling pathway.

Electroacupuncture improves cognitive ability following cerebral ischemia reperfusion injury via CaM-CaMKIV-CREB signaling in the rat hippocampus.

The aim of the present study was to investigate the effect of electroacupuncture (EA) on cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via the calmodulin (CaM)-calmodulin-dependent protein kinase type IV (CaMKIV)-cyclic adenosine monophosphate response elements binding protein (CREB) intracellular signaling pathway in the hippocampus. In total, 45 adult female Sprague-Dawley rats were randomly divided into three groups, namely the sham group, the middle cerebral artery occlusion (MCAO) group and the MCAO + EA group. Rats in the MCAO and MCAO + EA groups were modeled for post-stroke cognitive impairment. EA was performed at the Baihui and Shenting acupuncture points for 30 min/day for one week in the MCAO + EA group. Behavioral testing was analyzed using a step-down apparatus, while 2,3,5-triphenyl tetrazolium chloride was used to detect the infarct volume and lesion size. In addition, CaM activity was assessed by cyclic nucleotide-dependent phosphodiesterase analysis, and the protein expression levels of CaM, CaMKIV, phosphorylated (p)-CaMKIV, CREB and p-CREB were analyzed by western blot analysis. The cerebral I/R injured rat model in the MCAO group was established successfully with regard to the infarct volume and neuronal lesion size, as compared with the sham group. EA was demonstrated to effectively improve the cognitive ability, as measured by the step-down apparatus test, and decrease the infarct volume when compared with the MCAO group (P<0.05). The step-down apparatus test for the EA-treated rats revealed improved learning and reduced memory impairment when compared with the MCAO group. Furthermore, CaM activity and CaM protein expression levels in the MCAO + EA group were lower compared with those in the MCAO group (P<0.05). By contrast, the protein expression levels of CaMKIV, p-CaMKIV, CREB and p-CREB were significantly reduced in the MCAO group when compared with the sham group (P<0.05), although the expression levels increased following EA treatment when compared with the MCAO group (P<0.05). Therefore, cognitive repair benefited from EA, and the main intracellular signaling pathway in the hippocampus was mediated by CaM-CaMKIV-CREB. EA effectively inhibited the expression and activity of CaM, while further enhancing the expression of CaMKIV and CREB, and their associated phosphorylated functions.