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Background. The clinical efficacy of temporal three-needle therapy for stroke dysfunction has been previously demonstrated in China. However, the central mechanism of temporal three-needle therapy remains unclear. Temporal three-needle projects the sensory cortex and the motor cortex, which may impact the cortex function. Current studies seldom focus on it. Hence, according to the “scalp-cortex corresponding theory,” the underlying mechanism of temporal three-needle remains a domain for further research. Methods. This trial is designed to provide objective and visual evidence for the neuromodulatory effect and neuroimaging mechanism of temporal three-needle therapy for stroke patients. This ongoing study is a prospective, randomized, controlled, patient-assessor blind, single-center, neuroimaging trial involving two-parallel patient groups and a healthy control group. Forty eligible patients will be recruited from Shenzhen Nanshan District People’s Hospital and randomized into either the experimental group or the control group. Twenty healthy volunteers will be recruited in the healthy control group and undergo baseline magnetic resonance imaging scans without any intervention. Patients in the control group will receive acupuncture at Dingnieqianxiexian (MS6), in addition to basic medicine and rehabilitative treatments. Patients in the experimental group will receive temporal three-needle therapy plus basic medicine and rehabilitative treatments 5 days per week, 10 sessions over two consecutive weeks. The primary outcome is resting-state functional connectivity, and the secondary outcomes are regional homogeneity, amplitude of low-frequency fluctuations, Fugl–Meyer assessment of the upper limb, and modified Barthel Index. All outcome measures will be assessed at baseline and after 2 weeks of intervention. Discussion. The results will explore the neuromodulatory effects and illustrate the central mechanism of temporal three-needle treatment from the network-level viewpoint of sensorimotor network functional plasticity and promote widespread application in real-world practice. This trial was registered at Chinese Clinical Trial Registry on 14 March 2018 with ChiCTR1800015209.

Previous fundamental and clinical research has shown that electroacupuncture (EA) at the acupoints of Quchi (LI11) and Zusanli (ST36) can successfully alleviate motor dysfunction following stroke. Additionally, it has been discovered that gut microbiota and their metabolites play an essential role in stroke. However, the relationship between the metabolites of gut microbiota and the efficacy of EA is still unclear. Therefore, the aim of this study was to evaluate the mechanism of EA at LI11 and ST36 in the treatment of motor dysfunction after middle cerebral artery occlusion/reperfusion (MCAO/R) in model rats by comparing the differences and correlation between different short-chain fatty acids (SCFAs) and the recovery of motor function. The results indicated that EA at LI11 and ST36 acupoints enhanced the neurological function, motor function, and infarct volume of MCAO/R rats. The levels of acetic acid, propionic acid, and total SCFAs were considerably lower in the MCAO/R group than in the sham group ( P < 0.05 ). Acetic acid, propionic acid, and total SCFA concentrations were substantially higher in the MCAO/R + EA group than in the MCAO/R group ( P < 0.05 ). Finally, Pearson correlation analysis revealed that the propionic acid concentration was substantially favorably connected with the duration on the rotarod ( r = 0.633 and P < 0.05 ) and highly negatively correlated with the modified neurological severity score (mNSS) ( r = − 0.698 and P < 0.05 ) and the percentage of cerebral infarct volume ( r = − 0.729 and P < 0.05 ). Taken together, these findings indicate that the increase in propionic acid may be one of the mechanisms and targets of EA at LI11 and ST36 acupoints to improve poststroke motor dysfunction in MCAO/R rats.

Background To evaluate whether electroacupuncture (EA) treatment at LI11 and ST36 could reduce motor impairments and enhance brain functional recovery in a rat model of ischemic stroke. Methods A rat model of middle cerebral artery occlusion (MCAO) was established. EA at LI11 and ST36 was started at 24 h (MCAO + EA group) after ischemic stroke modeling. Untreated model (MCAO) and sham-operated (Sham) groups were included as controls. The neurological deficits of all groups were assessed using modified neurologic severity scores (mNSS) at 24 h and 14 days after MCAO. To further investigate the effect of EA on infarct volume and brain function, functional magnetic resonance imaging was used to estimate the size of the brain lesions and neural activities of each group at 14 days after ischemic stroke. Results EA treatment of MCAO rats led to a significant reduction in the infarct volumes accompanied by functional recovery, reflected in improved mNSS outcomes and motor functional performances. Furthermore, functional connectivity between the left motor cortex and left cerebellum posterior lobe, right motor cortex, left striatum and bilateral sensory cortex were decreased in MCAO group but increased after EA treatment. Conclusion EA at LI11 and ST36 could enhance the functional connectivity between the left motor cortex and the motor function-related brain regions, including the motor cortex, sensory cortex and striatum, in rats. EA exhibits potential as a treatment for ischemic stroke.

This study investigated the effects of Tai Chi compared with no exercise control on the cerebral hemodynamic parameters and other health-related factors in community older adults at risk of ischemic stroke. A total of 170 eligible participants were randomly allocated to Tai Chi or control group. The cerebral hemodynamic parameters and physical fitness risk factors of cardiovascular disease were measured at baseline, 12 weeks, and 24 weeks. After the 12-week intervention, Tai Chi significantly improved the minimum of blood flow velocity (BFVmin); BFVmean; pulsatility index and resistance index of the right anterior cerebral artery; and BFVmax, BFVmin, and BFVmean parameters of the right middle cerebral artery. Tai Chi training also decreased triglyceride, fasting blood glucose, and homocysteine levels, and improved balance ability. Therefore, the supervised 12-week Tai Chi exercise had potential beneficial effects on cerebral hemodynamics, plasma risk factors, and balance ability in older community adults at risk of ischemic stroke.

To evaluate the effect of tai chi exercise on cardiac and static lung function for older community-dwelling adults at risk of ischemic stroke. 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. 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. 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)

The primary objective of this review article was to summarize comprehensive information related to the neuropharmacological activity, mechanisms of action, toxicity, and safety of salidroside in medicine. A number of studies have revealed that salidroside exhibits neuroprotective activities, including anti-Alzheimer’s disease, anti-Parkinson’s disease, anti-Huntington’s disease, anti-stroke, anti-depressive effects, and anti-traumatic brain injury; it is also useful for improving cognitive function, treating addiction, and preventing epilepsy. The mechanisms underlying the potential protective effects of salidroside involvement are the regulation of oxidative stress response, inflammation, apoptosis, hypothalamus-pituitary-adrenal axis, neurotransmission, neural regeneration, and the cholinergic system. Being free of side effects makes salidroside potentially attractive as a candidate drug for the treatment of neurological disorders. It is evident from the available published literature that salidroside has potential use as a beneficial therapeutic medicine with high efficacy and low toxicity to the central nervous system. However, the definite target protein molecules remain unclear, and clinical trials regarding this are currently insufficient; thus, guidance for further research on the molecular mechanisms and clinical applications of salidroside is urgent.

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.

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

ObjectiveThe aim of this study was to identify the clinical efficacy of acupuncture in combination with RehaCom cognitive training in poststroke patients with cognitive dysfunction.Methods/DesignThis study was a 2 × 2 factorial design randomized controlled trial comparing acupuncture, computer-assisted cognitive rehabilitation, and the usual treatment by per-protocol analysis. The trial was completed by 204 stroke patients, including 49 patients in a control group, 52 patients in an acupuncture treatment group, 51 patients in a RehaCom training group, and 52 patients in an acupuncture combined with RehaCom group. All of the patients accepted basic treatment and health education. The interventions continued for 12 weeks (30 minutes per day, 5 days per week). The relative cognitive and functional outcomes were measured at baseline and 12 weeks (at the end of intervention) using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Functional Independence Measure (FIM) scales.ResultsAfter 12 weeks of treatment, the functional statuses of the patients in each of the 4 groups showed varying degrees of improvement. Multiple comparisons of the changes in the MMSE, MoCA, and FIM scores indicated that acupuncture combined with RehaCom cognitive training (ACR) had enhanced therapeutic effects on the functional statuses of the stroke patients (P

Ischemic stroke is a common cause of death due to obstructed blood supply of the brain. Despite growing numbers of research, etiology underlying ischemic stroke remains complex and elusive. Elevated plasma homocysteine has been known as a risk factor for ischemic stroke. Recently, a genome-wide association study reported association between rs548987 of SLC17A3 and homocysteine. Given existing relation between homocysteine and ischemic stroke, SLC17A3 was believed to be a promising candidate gene of ischemic stroke. Indeed, its association with ischemic stroke was previously reported in a western population. Herein, we used rs548987 as a candidate genetic variant of ischemic stroke and performed association analysis in a Chinese population with 918 ischemic stroke cases and 979 controls. Although rs548987 failed to show significant association with total ischemic stroke and large vessel disease subtype, the C allele of rs548987 showed significant association with small vessel disease subtype of ischemic stroke (OR=0.68, p=0.004). Our preliminary results suggested different genetic etiology underlying the two most common subtypes of ischemic stroke and provided additional evidence to understand contribution of homocysteine to the disease.

Stroke is a significant cause of morbidity and long-term disability globally. Detection of injured neuron is a prerequisite for defining the degree of focal ischemic brain injury, which can be used to guide further therapy. Here, we demonstrate the capability of two-photon microscopy (TPM) to label-freely identify injured neurons on unstained thin section and fresh tissue of rat cerebral ischemia-reperfusion model, revealing definite diagnostic features compared with conventional staining images. Moreover, a deep learning model based on convolutional neural network is developed to automatically detect the location of injured neurons on TPM images. We then apply deep learning-assisted TPM to evaluate the ischemic regions based on tissue edema, two-photon excited fluorescence signal intensity, as well as neuronal injury, presenting a novel manner for identifying the infarct core, peri-infarct area, and remote area. These results propose an automated and label-free method that could provide supplementary information to augment the diagnostic accuracy, as well as hold the potential to be used as an intravital diagnostic tool for evaluating the effectiveness of drug interventions and predicting potential therapeutics.

The aim of current study was to assess the effects of Baduanjin exercise on cerebrovascular function, cardiac structure and cardiac function, static pulmonary function, traditional risk factors of CVD and the related psychological outcomes in older community adults at risk for ischaemic stroke. A randomized controlled trial was conducted in three community between November 2013 and October 2015. Older community-dwelling adults (N = 170) were randomly allocated into either a Baduanjin training (5 × 60 min/weekly) or control group who kept their unaltered lifestyle during a 12-week intervention period. Primary (cerebral haemodynamic parameters) and secondary outcomes (cardiac structure, cardiac function, static pulmonary function, traditional risk factors and the related psychological outcomes) were measured at baseline, after a 12-week intervention period and after an additional 12-week follow-up period. After the 12-week intervention period and additional 12-week follow-up period, the Baduanjin exercise group displayed significant changes in most cerebral haemodynamic parameters compared to the control group: lower systolic blood pressure, diastolic blood pressure, plasma total cholesterol levels, waist circumference, hip circumference and waist/hip ratio; and improved mood, self-confidence, self-esteem, quality of life and sleep quality. A supervised 12-week Baduanjin exercise intervention was effective and safe in modulating cerebral haemodynamics, reducing blood pressure and improving anthropometric parameters and related psychological outcomes in older community adults at risk for ischaemic stroke.

Backgroud Tai Chi Chuan was used for stroke survivors with balance impairments. However, even a short-form of Tai Chi Chuan includes forms that make the exercise challenging for the stroke survivors. Tai Chi Yunshou (wave hands in the cloud) is the “mother” form and the fundamental form of all Tai Chi Chuan styles, which is considered more suitable and feasible for stroke survivors with balance impairments. So this study was designed to evaluate the effects of Tai Chi Yunshou exercise on community-based stroke patients with balance dysfunctions. Methods A total of 250 participants from 10 community health centers (5 per arm) were selected and randomly allocated into Tai Chi Yunshou exercise group (TC group) or a balance rehabilitation training group (control group) in an equal ratio. Participants in the TC group were received Tai Chi Yunshou exercise training five times per week for 12 weeks and those in control group were received balance rehabilitation training five times per week for 12 weeks. Outcome assessments including Berg Balance Scale (BBS), Time up to go test (TUGT), Modified Barthel Index (MBI) were measured at baseline, 4 weeks, 8 weeks, 12 weeks and followed-up 6 weeks (18 weeks), 12 weeks (24 weeks). Intention-to-treat analysis was performed. Analysis of variance of repeated measures was used to assess between-group differences. Results A total of 244 participants, 120 in the TC group and 124 in the rehabilitation group, were included in final analysis. There was no siginificant difference in Tai Chi Yunshou and balance rehabilitation training on the improvement of balance ability and mobility (P = 0.531 and P = 0.839, respectively) after adjustment for baseline. However, there was significant difference between two groups on improvement of motor funtion (P = 0.022), fear of falling (P

The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

OBJECTIVE To investigate how clinical experience and access to patient information regarding functional capability influence inter-rater reliability and validity of the Brief International Classification of Functioning, Disability, and Health Core Set for Stroke (ICF) assessment. METHODS Study 1 involved expert (clinical experience > 5 years) and novice (clinical experience

The aim of the present study was to investigate the neuroprotective mechanism of the miR-9-mediated activation of the nuclear factor (NF)-κB signaling pathway by electroacupuncture (EA) stimulation of the Quchi (LI11) and Zusanli (ST36) acupoints in a rat model of middle cerebral artery occlusion (MCAO). The present study demonstrated that EA alleviated the symptoms of neurological deficits and reduced the infarct volume in the rat brains. The expression of miR-9 in the peri-infarct cortex was increased in the EA group compared with the MCAO group, and the expression of NF-κB signaling pathway-associated factors, NF-κB p65, tumor necrosis factor (TNF)-α and interleukin (IL)-1β were reduced. Notably, miR-9 inhibitors were revealed to have the ability to suppress EA-alleviated cerebral inflammation and the expression of NF-κB downstream-related factors, NF-κB p65, TNF-α and IL-1β, and caused no alteration on the level of NF-κB upstream-related protein inhibitor of κBα, suggesting that the cerebral protective efficacy of EA targets miR-9-mediated NF-κB downstream pathway following ischemic stroke.

In a previous study by our group, we demonstrated that electroacupuncture (EA) activates the class I phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. There is considerable evidence that the downstream mammalian target of rapamycin complex 1 (mTORC1) plays an important role in autophagy following ischemic stroke. The aim of the present study was to determine whether EA exerts a neuroprotective effect through mTORC1-mediated autophagy following ischemia/reperfusion injury. Our results revealed that EA at the LI11 and ST36 acupoints attenuated motor dysfunction, improved neurological deficit outcomes and decreased the infarct volumes. The number of autophagosomes, autolysosomes and lysosomes was decreased following treatment with EA. Simultaneously, the levels of the autophagosome membrane maker, microtubule-associated protein 1 light chain 3 beta (LC3B)II/I, Unc-51-like kinase 1 (ULK1), autophagy related gene 13 Atg13) and Beclin1 (ser14) were decreased, whereas mTORC1 expression was increased in the peri-infarct cortex. These results suggest that EA protects against ischemic stroke through the inhibition of autophagosome formation and autophagy, which is mediated through the mTORC1-ULK complex-Beclin1 pathway.

BackgroundMonitoring the functional status of poststroke patients after they transition home is significant for rehabilitation. Mobile health (mHealth) technologies may provide an opportunity to reach and follow patients post discharge. However, the feasibility and validity of functional assessments administered by mHealth technologies are unknown.ObjectiveThis study aimed to evaluate the feasibility, validity, and reliability of functional assessments administered through the videoconference function of a mobile phone–based app compared with administration through the telephone function in poststroke patients after rehabilitation hospitalization.MethodsA randomized controlled trial was conducted in a rehabilitation hospital in Southeast China. Participants were randomly assigned to either a videoconference follow-up (n=60) or a telephone follow-up (n=60) group. We measured the functional status of participants in each group at 2-week and 3-month follow-up periods. Half the participants in each group were followed by face-to-face home visit assessments as the gold standard. Validity was assessed by comparing any score differences between videoconference follow-up and home visit assessments, as well as telephone follow-up and home visit assessments. Reliability was assessed by computing agreements between videoconference follow-up and home visit assessments, as well as telephone follow-up and home visit assessments. Feasibility was evaluated by the levels of completion, satisfaction, comfort, and confidence in the 2 groups.ResultsScores obtained from the videoconference follow-up were similar to those of the home visit assessment. However, most scores collected from telephone administration were higher than those of the home visit assessment. The agreement between videoconference follow-up and home visit assessments was higher than that between telephone follow-up and home visit assessments at all follow-up periods. In the telephone follow-up group, completion rates were 95% and 82% at 2-week and 3-month follow-up points, respectively. In the videoconference follow-up group, completion rates were 95% and 80% at 2-week and 3-month follow-up points, respectively. There were no differences in the completion rates between the 2 groups at all follow-up periods (X21=1.6, P=.21 for 2-week follow-up; X21=1.9, P=.17 for 3-month follow-up). Patients in the videoconference follow-up group perceived higher confidence than those in the telephone follow-up group at both 2-week and 3-month follow-up periods (X23=6.7, P=.04 for 2-week follow-up; X23=8.0, P=.04 for 3-month follow-up). The videoconference follow-up group demonstrated higher satisfaction than the telephone follow-up group at 3-month follow-up (X23=13.9; P=.03).ConclusionsThe videoconference follow-up assessment of functional status demonstrates higher validity and reliability, as well as higher confidence and satisfaction perceived by patients, than the telephone assessment. The videoconference assessment provides an efficient means of assessing functional outcomes of patients after hospital discharge. This method provides a novel solution for clinical trials requiring longitudinal assessments.Trial Registrationchictr.org.cn: ChiCTR1900027626; http://www.chictr.org.cn/edit.aspx?pid=44831&htm=4.

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 (18)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.

BACKGROUND Previous studies suggested that inhibition of apoptosis prevents the dysfunction of ischemia-reperfusion injury. In the pathogenesis of ischemia-reperfusion injury, JNK/ERK1/2 and p38 play an essential role in regulation of cell apoptosis. Electroacupuncture (EA), a form of acupuncture, has demonstrated superiority in preventing ischemia-reperfusion injury, but the underlying mechanism is unclear. In the present study, we explored the effects of electroacupuncture at Shenting (GV24) and Baihui (GV20) acupoints on focal cerebral ischemia-reperfusion (MCAO) rats, and explored whether JNK/ERK1/2- and p38-mediated cell apoptosis are involved. MATERIAL AND METHODS The rats were divided into a sham operation control group, an ischemia group, and an electroacupuncture group with acupuncture applied for 10 days (30 min per day). TTC staining was used to calculate the ischemic brain volume. TUNEL staining and transmission electron microscopy were used to detect cell apoptosis. Western blot analysis and Bio-Plex were used to detect JNK, p38, ERK1/2, Bcl-2, and Bax protein expression. RESULTS We found that electroacupuncture at day 10 significantly reduced cerebral infarction. In addition, electroacupuncture suppressed activation of JNK and p38, while enhancing the activation of ERK1/2 in the peri-ischemic regions. Consequently, the effect of electroacupuncture on these pathways resulted in the inhibition of apoptosis, which was demonstrated by TUNEL and transmission electron microscopy. We found that electroacupuncture upregulated the anti-apoptotic Bcl-2/Bax ratio in peri-ischemic regions. CONCLUSIONS Our findings suggest that inhibition of cell apoptosis via regulating multiple signaling pathways might be a mechanism whereby electroacupuncture has a positive therapeutic effect on post-stroke impairment.

Background Upper limb dysfunction is common after stroke, posing an important challenge for post-stroke rehabilitation. The clinical efficacy of acupuncture for the recovery of post-stroke upper limb function has been previously demonstrated. Mirror therapy (MT) has also been found to be effective. However, the effects of acupuncture and MT have not been systematically compared. This trial aims to elucidate the synergistic effects of acupuncture and MT on upper limb dysfunction after stroke. Methods A 2 × 2 factorial randomized controlled trial will be conducted at the rehabilitation hospitals affiliated with Fujian University of Traditional Chinese Medicine. A total of 136 eligible subjects will be randomly divided into acupuncture treatment (AT), MT, combined treatment, and control groups in a 1:1:1:1 ratio. All subjects will receive conventional treatment. The interventions will be performed 5 days per week for 4 weeks. AT, MT, and combined treatment will be performed for 30 min per day (combined treatment: AT 15 min + MT 15 min). The primary outcomes in this study will be the mean change in scores on both the FMA and WMFT from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The secondary outcomes are the mean change in the scores on the Visual Analogue Scale, Stroke Impact Scale, and modified Barthel index. Medical abstraction of adverse events will be assessed at each visit. Discussion The results of this trial will demonstrate the synergistic effect of acupuncture and MT on upper limb motor dysfunction after stroke. In addition, whether AT and MT, either combined or alone, are more effective than the conventional treatment in the management of post-stroke upper limb dysfunction will also be determined. Trial registration Chinese Clinical Trial Registry: ChiCTR-IOR-17011118. Registered on April 11, 2017. Version number: 01.2016.09.1. Electronic supplementary material The online version of this article (10.1186/s13063-018-2585-8) contains supplementary material, which is available to authorized users.

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.

Electro-acupuncture (EA) is a novel therapy based on combining traditional acupuncture with modern electrotherapy, and it is currently being investigated as a treatment for ischemic stroke. In the present study, we aimed to investigate the mechanisms through which EA regulates the proliferation of neural progenitor cells (NPCs) in the cortical peri‑infarct area after stroke. The neuroprotective effects of EA on ischemic rats were evaluated by determining the neurological deficit scores and cerebral infarct volumes. The proliferation of the NPCs and the activation of the Wnt/β‑catenin signaling pathway in the cortical peri‑infarct area were examined. Our results revealed that EA significantly alleviated neurological deficits, reduced the infarct volume and enhanced NPC proliferation [nestin/glial fibrillary acidic protein (GFAP)‑double positive] in the cortex of rats subjected to middle cerebral artery occlusion (MCAO). Moreover, the Wnt1 and β‑catenin mRNA and protein levels were increased, while glycogen synthase kinase‑3 (GSK3) transcription was suppressed by EA. These results suggest that the upregulatory effects of EA on the Wnt/β‑catenin signaling pathway may promote NPC proliferation in the cortical peri-infarct area after stroke, consequently providing a therapeutic effect against cerebral ischemia.

The aim of the present study was to investigate the mechanisms underlying the neuroprotective and antispastic effects of Gua Lou Gui Zhi decoction (GLGZD) in a rat model of middle cerebral artery occlusion (MCAO). The MCAO rats were treated with GLGZD (14.3 g/kg body weight) once a day for a period of seven days. Neurological deficit scores and screen tests were analyzed every other day. Following treatment with GLGZD for 7 days, the ischemic infarct volume of the rat brains was measured using 2,3,5‑triphenyl tetrazolium chloride staining. Reverse transcription‑polymerase chain reaction was performed in order to determine the mRNA expression levels of γ‑amino butyric acid B (γ‑GABAB) receptor (R) in the cortical infarct region. Furthermore, the protein expression levels of GABAB R were detected in the cortical infarct region by western blot analysis. Following 7 days, treatment with GLGZD significantly ameliorated the neurological defects and cerebral infarction in the MCAO rats. In addition, treatment with GLGZD ameliorated motor performance in the MCAO rats, as determined by screen tests. Furthermore, GLGZD was able to upregulate the mRNA and protein expression levels of GABAB1 R and GABAB2 R in the ischemic cerebral cortex. The results of the present study suggested that GLGZD may exert neuroprotective and antispastic effects in a cerebral ischemia model, through upregulating the expression of GABAB R.

Background.Stroke is a major healthcare problem with serious long-term disability and is one of the leading causes of death in the world. Prevention of stroke is considered an important strategy.Methods.Seven electronic databases were searched.Results.36 eligible studies with a total of 2393 participants were identified. Primary outcome measures, TCC exercise combined with other intervention had a significant effect on decreasing the incidence of nonfatal stroke (n=185, RR = 0.11, 95% CI 0.01 to 0.85,P=0.03) and CCD (n=125, RR = 0.33, 95% CI 0.11 to 0.96,P=0.04). For the risk factors of stroke, pooled analysis demonstrated that TCC exercise was associated with lower body weight, BMI, FBG level, and decreasing SBP, DBP, plasma TC, and LDL-C level regardless of the intervention period less than half a year or more than one year and significantly raised HDL-C level in comparison to nonintervention. Compared with other treatments, TCC intervention on the basis of the same other treatments in patients with chronic disease also showed the beneficial effect on lowering blood pressure.Conclusion.The present systematic review indicates that TCC exercise is beneficially associated with the primary prevention of stroke in middle-aged and elderly adults by inversing the high risk factors of stroke.

Ethnopharmacological relevance Gualou Guizhi decoction (GLGZD) prescribed in traditional Chinese medicine has been reported to have protective effects on ischemic stroke. The present study is to investigate the therapeutic effect of GLGZD on ischemic stroke and explore its mode of action. Materials and methods GLGZD was studied on transient middle cerebral artery occlusion (MCAO) followed by reperfusion in viv o, as well as on hippocampal primary neuron c ultures in vitro . Results In viv o, it was shown that GLGZD treatment for 7 days could ameliorate transient middle cerebral artery occlusion (MCAO)-induced neurological deficit, histopathology changes and decrease infarct area. Further study demonstrated that GLGZD inhibited over-activation of astrocytes and apoptosis of neurons and GLGZD promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, the in vitro study revealed that GLGZD treatment protected against NMDA-induced cell apoptosis and neuronal loss, and promoted up-regulation of neuronal specific marker NeuN. Conclusions Taken together, the present study demonstrates that GLGZD produces a protection in the MCAO model rats via inhibiting over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN and MAP-2. Our study reveals that GLGZD might be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

According to Traditional Chinese Medicine there is an optimum time to administer acupuncture at a particular acupoint. The present study used functional magnetic resonance imaging to investigate the timing effects of acupuncture at the Zusanli (ST36) acupoint. A total of 10 healthy volunteers and 10 post-stroke patients were recruited. The subjects received acupuncture stimulation at ST36 during two time periods: between 7:00 a.m. and 9:00 a.m. (the AM condition) and between 3:00 p.m. and 5:00 p.m. (the PM condition), seven days later. Blood oxygenation level-dependent signals were captured while the patient was receiving the acupuncture stimulation. The results showed a stronger activation in the AM condition than in the PM condition in both healthy and stroke subjects. The significant regions in the healthy subjects included the prefrontal cortex, cingulum, thalamus and cerebellum; for the stroke patients, the significant regions were the cuneus, supplementary motor area and inferior parietal gyrus. Timing can therefore modulate brain activation patterns during acupuncture in healthy subjects and stroke patients; however, the modulation effect appears to differ between the two subject groups. Further studies are required to explore the timing effects of acupuncture at different acupoints in different populations.

Background Evidence from quantitative studies suggest that Tai Chi produces a variety of health-related benefits, but few qualitative studies have investigated how older adults perceive the benefit of Tai Chi. The objective of the current study was to qualitatively evaluate the perceived benefits of Tai Chi practice among community older population. Methods This study was conducted with participants from a trial examining the effects of a 12-week Tai Chi training on ischemic stroke risk in community older adults (n = 170). A total of 20 participants were randomly selected from a convenience sample of participants who had completed 12-week Tai Chi training (n = 68) were interviewed regarding their perceived benefit on physical and mental health and whether Tai Chi exercise was suitable for the elderly. Results All participants agreed that Tai Chi training could relax their body and make them comfortable. Most of them thought Tai Chi training could promote physical health, including relieving pain, enhancing digestion, strengthening immunity, enhancing energy and improving sleep quality, enhancing their mental and emotional state (e.g. improving mood and reducing anxiety, improving concentration and promoting interpersonal relationship). Most of participants also agreed that Tai Chi exercise was appropriate for community older people. Three primary themes emerged from content analysis: Improving physical health; Enhancing mental and emotional state; Conforming with the request of the elderly. Conclusion The findings indicate that regular Tai Chi exercise may have positive benefits in terms of improved physical health and mental state among community elderly population, and may be useful and feasible body-mind exercise to community elderly population for its positive effects and advantages. Trial registration ChiCTR ChiCTR-TRC-13003601. Registered 23 July 2014. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1694-3) contains supplementary material, which is available to authorized users.

Objective To evaluate whether electro-acupuncture (EA) treatment at acupoints of Zusanli (ST 36) and Quchi (LI 11) could reduce motor impairments and enhance brain functional recovery in rats with ischemic stroke. Materials and Methods A rat model of middle cerebral artery occlusion (MCAO) was established. EA at ST 36 and LI 11was started at 24 hours (MCAO + EA group) after ischemic stroke. The nontreatment (MCAO) and sham-operated control (SC) groups were included as controls. The neurologic deficits of all groups were assessed by Zea Longa scores and the modified neurologic severity scores on 24 hours and 8 days after MCAO. To further investigate the effect of EA on infract volume and brain function, magnetic resonance imaging was used to estimate the brain lesion and brain neural activities of each group at 8 days after ischemic stroke. Results Within 1 week after EA treatment, the neurologic deficits were significantly alleviated, and the cerebral infarctions were improved, including visual cortex, motor cortex, striatum, dorsal thalamus, and hippocampus. Furthermore, whole brain neural activities of auditory cortex, lateral nucleus group of dorsal thalamus, hippocampus, motor cortex, orbital cortex, sensory cortex, and striatum were decreased in MCAO group, whereas that of brain neural activities were increased after EA treatment, suggesting these brain regions are in accordance with the brain structure analysis. Conclusion EA at ST 36 and LI 11 could enhance the neural activity of motor function-related brain regions, including motor cortex, dorsal thalamus, and striatum in rats, which is a potential treatment for ischemia stroke.

MircoRNAs (miRs) have been implicated in learning and memory, by regulating LIM domain kinase (LIMK1) to induce synaptic-dendritic plasticity. The study aimed to investigate whether miRNAs/LIMK1 signaling was involved in electroacupuncture- (EA-) mediated synaptic-dendritic plasticity in a rat model of middle cerebral artery occlusion induced cognitive deficit (MICD). Compared to untreatment or non-acupoint-EA treatment, EA at DU20 and DU24 acupoints could shorten escape latency and increase the frequency of crossing platform in Morris water maze test. T2-weighted imaging showed that the MICD rat brain lesions were located in cortex, hippocampus, corpus striatum, and thalamus regions and injured volumes were reduced after EA. Furthermore, we found that the density of dendritic spine and the number of synapses in the hippocampal CA1 pyramidal cells were obviously reduced at Day 14 after MICD. However, synaptic-dendritic loss could be rescued after EA. Moreover, the synaptic-dendritic plasticity was associated with increases of the total LIMK1 and phospho-LIMK1 levels in hippocampal CA1 region, wherein EA decreased the expression of miR-134, negatively regulating LIMK1 to enhance synaptic-dendritic plasticity. Therefore, miR-134-mediated LIMK1 was involved in EA-induced hippocampal synaptic plasticity, which served as a contributor to improving learning and memory during the recovery stage of ischemic stroke.

Ischemic stroke, the second leading cause of death worldwide, leads to excessive glutamate release, over-activation of N-methyl-D-aspartate receptor (NMDAR), and massive influx of calcium (Ca2+), which may activate calpain and caspase-3, resulting in cellular damage and death. Memantine is an uncompetitive NMDAR antagonist with low-affinity/fast off-rate. We investigated the potential mechanisms through which memantine protects against ischemic stroke in vitro and in vivo. Middle cerebral artery occlusion-reperfusion (MCAO) was performed to establish an experimental model of ischemic stroke. The neuroprotective effects of memantine on ischemic rats were evaluated by neurological deficit scores and infarct volumes. The activities of calpain and caspase-3, and expression levels of microtubule-associated protein-2 (MAP2) and postsynaptic density-95 (PSD95) were determined by Western blotting. Additionally, Nissl staining and immunostaining were performed to examine brain damage, cell apoptosis, and neuronal loss induced by ischemia. Our results show that memantine could significantly prevent ischemic stroke-induced neurological deficits and brain infarct, and reduce ATP depletion-induced neuronal death. Moreover, memantine markedly suppressed the activation of the calpain-caspase-3 pathway and cell apoptosis, and consequently, attenuated brain damage and neuronal loss in MCAO rats. These results provide a molecular basis for the role of memantine in reducing neuronal apoptosis and preventing neuronal damage, suggesting that memantine may be a promising therapy for stroke patients.

The extracellular signal-regulated kinase (ERK) pathway, a critical mediator of cell proliferation, is activated in cerebral ischemia/reperfusion (I/R) injury and is therefore a key target in the treatment of ischemic stroke. Acupuncture has long been used in China to clinically treat stroke. However, the precise mechanism of its neuroprotective activities remains largely unknown. In the present study, a focal cerebral I/R-injured rat model was used to evaluate the in vivo therapeutic efficacy of electroacupuncture (EA) and investigate the underlying molecular mechanisms. EA significantly ameliorated neurological deficits and cerebral infarction in cerebral I/R-injured rats. Moreover, EA significantly increased the phosphorylation levels of ERK, as well as the protein expression levels of Ras, cyclin D1 and cyclin-dependent kinase (CDK)4. Consequently, EA-mediated activation of the ERK pathway resulted in the stimulation of cerebral cell proliferation. The present data suggest that EA at the Quchi and Zusanli acupoints exerts a neuroprotective effect in ischemic stroke via the activation of ERK signaling.

Background Ischemic stroke is a life-threatening condition due to obstructed blood supply of the brain. Elevation of plasma C-reactive protein, an important inflammatory marker, was known to associate with increased risk of ischemic stroke. Previous studies reported association between genetic variants of HNF1A and plasma level of C-reactive protein. The HNF1A gene encodes a hepatocyte transcription factor which might have regulatory effects on C-reactive protein synthesis in liver. Therefore, the C-reactive protein associated gene HNF1A seems to be a promising candidate gene for ischemic stroke. Results We used HNF1A as a candidate gene of ischemic stroke and evaluated seven common variants of HNF1A for their contribution to ischemic stroke. The association analysis of HNF1A variants with ischemic stroke was performed in a Chinese population with 918 cases and 979 controls. For total ischemic stroke and large vessel disease subtype, none of variants exceeded significant threshold. For small vessel disease subtype of ischemic stroke, the G allele of rs7953249 showed nominal association (OR = 0.82, p = 0.04) after data adjustment for conventional risk factors. However, our preliminary results did not survived bonferroni correction for multiple comparisons. Conclusions Common genetic variants of HNF1A showed nominal association with small vessel disease subtype of ischemic stroke though not survived bonferroni correction for multiple comparisons. The association between HNF1A and ischemic stroke is limited by small effects of individual SNPs. Our study provided additional genetic evidences to understand the role of HNF1A gene and C-reactive protein underlying ischemic stroke. Electronic supplementary material The online version of this article (doi:10.1186/s12881-016-0313-3) contains supplementary material, which is available to authorized users.

Background Cognitive impairments are highly prevalent in stroke survivors and can substantially affect their physical rehabilitation and quality of life. The management of these impairments currently remains limited, but increasing studies reported the effect of aerobic exercise on cognitive performance in patients suffering from stroke. The purpose of this review was to assess the effects of aerobic exercise on cognitive function following stroke. Methods Seven electronic databases (China National Knowledge Infrastructure [CNKI], Chinese Science and Technology Periodical Database [VIP], Wanfang, China Biology Medicine disc [CBM], Science Citation Index [SCI], EMBASE, and PubMed) were searched from their inception to May 31, 2015, for the effects of aerobic exercise on cognitive ability compared to usual physical activity in stroke survivors. RevMan V5.3 (The Nordic Cochrane Centre) was used to analyze the data and to evaluate the methodological quality of the included studies. Results Ten eligible studies including 394 participants were identified. Six studies showed that aerobic exercise significantly improved global cognitive ability in stroke survivors. Four studies reported aerobic exercise to be beneficial in improving memory, but only one showed statistical significance. Two studies investigated the effects of aerobic exercise on attention, and one showed a significant improvement. One study reported a significant benefit of aerobic exercise on visuospatial ability in stroke survivors. No adverse events were reported in the included studies. Conclusions Aerobic exercise may have a positive effect on improving global cognitive ability and a potential benefit on memory, attention, and the visuospatial domain of cognition in stroke survivors. However, further large, rigorously designed trials are needed to confirm these findings.

The PI3K/Akt pathway, a critical mediator of cell survival, is suppressed in cerebral ischemia/reperfusion (I/R) injury; therefore, it is a major focus in treatment of ischemic stroke. Acupuncture has long been used in China to clinically treat stroke. However, the precise mechanism of its neuroprotective activities remains largely unknown. Using a focal cerebral I/R injured rat model, in the present study we evaluated the in vivo therapeutic efficacy of electroacupuncture and investigated the underlying molecular mechanisms. We found that electroacupuncture at Quchi (LI11) and Zusanli (ST36) acupoints on the contralateral paralyzed limb significantly improved neurological deficits and cerebral infarction. In addition, electroacupuncture profoundly activated PI3K/Akt signaling in ischemic cerebral tissues. Consequently, the upregulatory effect of electroacupuncture on PI3K/Akt activation resulted in the inhibition of cerebral cell apoptosis. Moreover, electroacupuncture increased the serum secretion levels of the PI3K activators BDNF and GDNF, as well as upregulated the anti-apoptotic Bcl-2/Bax ratio in ischemic cerebrum. Our data suggest that electroacupuncture at Quchi and Zusanli acupoints exerts neuroprotective function in ischemic stroke via activation of the PI3K/Akt pathway.

Introduction Controlling risk factors with regular exercise is effective and cost-effective for the primary prevention of ischaemic stroke. As a traditional Chinese form of exercise, Tai Chi might be beneficial in decreasing ischaemic stroke, but the evidence remains insufficient. We hypothesise that elderly community adults with risk factors for ischaemic stroke will decrease their ischaemic stroke risk by improving cerebral haemodynamic parameters, cardiopulmonary function, motor function, plasma risk indices, physical parameters or psychological outcomes after receiving 12 weeks of regular Tai Chi training compared with those who maintained their original physical activities. Therefore, we designed a randomised controlled trial that will systematically evaluate the protective effects of Tai Chi exercise on ischaemic stroke risk in an elderly community population with risk factors for ischaemic stroke. Methods and analysis A total of 170 eligible participants were randomly allocated into either the Tai Chi training group or the usual physical activity group. This paper reports on the design, intervention development and baseline characteristics of the participants. There were no significant differences between comparison groups in demographic characteristics or the baseline data of primary or secondary outcomes. Participants in the Tai Chi training group will receive 12 weeks of Tai Chi training with a frequency of 5 days/week and 60 min/day, while those in the usual physical activities group will maintain their original activities. Primary and secondary outcomes will be measured at the 12-week and 24-week follow-ups. Ethics and dissemination Ethical approval has been obtained from the Medical Ethics Committee of The Affiliated People9s Hospital of Fujian University of Traditional Chinese Medicine (number 2013-020-02). The findings of this study will be communicated to healthcare professionals, participants and the public through peer-reviewed publications or scientific conferences. Trial registration number ChiCTR-TRC-13003601; Pre-results.

Introduction Poststroke cognitive impairment is one of the most common complications in stroke survivors, and >65% of these patients suffer from cognitive impairment at 12 months following onset, which strongly affects the rehabilitation of their motor function and quality of life. Therefore, it is important to improve the cognitive ability of stroke survivors. As an important component of traditional Chinese Qigong exercises, characterised by the coordination of mind and body with a low exercise intensity, Baduanjin has the potential benefit of improving cognitive ability for patients who had a stroke with cognitive impairment. The primary purpose of this study is to investigate the effectiveness and safety of Baduanjin training on the cognitive function of stroke survivors. Method and analysis This study is designed as a randomised, two-arm parallel controlled trial with allocation concealment and assessors blinding. A total of 48 participants will be recruited and randomly allocated into the Baduanjin exercise intervention or control group. Baduanjin intervention will last 24 weeks with a frequency of 3 days a week and 40 min a day. Global cognitive function and the specific domains of cognition (ie, memory, processing speed, execution, attention and visuospatial ability) will be measured at baseline, 8, 16 and, 24 weeks after intervention and after an additional 4-week follow-up period, while the motor function and quality of life will be measured at baseline, 24 weeks after intervention and after an additional 4-week follow-up period. Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital (approval number: 2016KY-022–01). The findings will be disseminated through peer-reviewed publications and at scientific conferences. Trial registration number ChiCTR-INR-16009364; Pre-results.

Background Post-stroke cognitive impairment seriously affects the quality of life and functional rehabilitation of patients with stroke. Objective To examine the effects of electroacupuncture (EA) at GV20 and GV24 on cognitive impairment and apoptosis including expression of apoptosis-related genes Bcl-2 and Bax in a rat model of cerebral ischaemia-reperfusion (IR) induced by middle cerebral artery occlusion (MCAO). Methods Thirty-five Sprague-Dawley rats were allocated to a sham operation control group (SC group, n=10) or underwent surgery and MCAO (n=25). Postoperatively the latter group was randomly subdivided into EA or untreated (IR) groups. Cognitive impairment was assessed using the Morris water maze (MWM). Apoptosis was examined by detection of Bcl-2 and Bax expression in the cerebral cortex. Results The EA group had significantly decreased neurological deficit scores compared to the IR group (pConclusions These findings suggest that EA ameliorates cognitive impairment of rats with IR injury by modulating Bcl-2 and Bax expression.

Aims Electroacupuncture (EA) is one of the safety and effective therapies for improving neurological and sensorimotor impairment via blockade of inappropriate inflammatory responses. However, the mechanisms of anti-inflammation involved is far from been fully elucidated. Main methods Focal cerebral ischemic stroke was administered by the middle cerebral artery occlusion and reperfusion (MCAO/R) surgery. The MCAO/R rats were accepted EA treatment at the LI 11 and ST 36 acupoints for consecutive 3 days. The neurological outcome, animal behaviors test and molecular biology assays were used to evaluate the MCAO/R model and therapeutic effect of EA. Key findings EA treatment for MCAO rats showed a significant reduction in the infarct volumes accompanied by functional recovery in mNSS outcomes, motor function performances. The possible mechanisms that EA treatment attenuated the over-activation of Iba-1 and ED1 positive microglia in the peri-infract sensorimotor cortex. Simultaneously, both tissue and serum protein levels of the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were decreased by EA treatment in MCAO/R injured rats. The levels of inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) were decreased in the peri-infract sensorimotor cortex and blood serum of MCAO/R injured rats after EA treatment. Furthermore, we found that EA treatment prevented from the nucleus translocation of NF-κB p65 and suppressed the expression of p38 mitogen-activated protein kinase (p38 MAPK) and myeloid differentiation factor 88 (MyD88) in the peri-infract sensorimotor cortex. Significance The findings from this study indicated that EA improved the motor impairment via inhibition of microglia-mediated neuroinflammation that invoked NF-κB p65, p38 MAPK and MyD88 produced proinflammatory cytokine in the peri-infract sensorimotor cortex of rats following ischemic stroke.

Paeoniflorin (PF) is a principal bioactive component, which exhibits many pharmacological effects, including protection against ischemic injury. This paper aimed to investigate the protective effect of PF both in vivo and in vitro. Middle cerebral artery occlusion (MCAO) was performed on male Sprague-Dawley (SD) rat for 2 h, and different doses of PF or vehicle were administered 2 h after reperfusion. Rats were sacrificed after 7 days treatment of PF/vehicle. PF treatment for 7 days ameliorated MCAO-induced neurological deficit and decreased the infarct area. Further study demonstrated that PF inhibited the over-activation of astrocytes and apoptosis of neurons, and PF promoted up-regulation of neuronal specific marker neuron-specific nuclear (NeuN) and microtubule-associated protein 2 (MAP-2) in brain. Moreover, NMDA-induced neuron apoptosis was employed. The in vitro study revealed that PF treatment protected against NMDA-induced cell apoptosis and neuronal loss via up-regulation of neuronal specific marker NeuN, MAP-2 and Bcl-2 and the down-regulation Bax. Taken together, the present study demonstrates that PF produces its protective effect by inhibiting the over-activation of astrocytes, apoptosis of neurons and up-regulation of neuronal specific marker NeuN, MAP-2, and B-cell lymphoma-2 (Bcl-2), and down-regulation Bax. Our study reveals that PF may be a potential neuroprotective agent for stroke and can provide basic data for clinical use.

A majority of stroke survivors present with cognitive impairments. Attention disturbance, which leads to impaired concentration and overall reduced cognitive functions, is strongly associated with stroke. The clinical efficacy of acupuncture with Baihui (GV20) and Shenting (GV24) as well as computer-assisted cognitive training in stroke and post-stroke cognitive impairment have both been demonstrated in previous studies. To date, no systematic comparison of these exists and the potential beneficial effects of a combined application are yet to be examined. The main objective of this pilot study is to evaluate the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The second objective is to test the effects of a combined cognitive intervention that incorporates computer-assisted cognitive training and acupuncture (ACoTrain). An international multicentre, single-blinded, randomised controlled pilot trial will be conducted. In a 1:1:1 ratio, 60 inpatients with post-stroke cognitive dysfunction will be randomly allocated into either the acupuncture group, the computer-assisted cognitive training group, or the ACoTrain group in addition to their individual rehabilitation programme. The intervention period of this pilot trial will last 4 weeks (30 minutes per day, 5 days per week, Monday to Friday). The primary outcome is the test battery for attentional performance. The secondary outcomes include the Trail Making Test, Test des Deux Barrages, National Institute of Health Stroke Scale, and Modified Barthel Index for assessment of daily life competence, and the EuroQol Questionnaire for health-related quality of life. This trial mainly focuses on evaluating the effects of computer-assisted cognitive training compared to acupuncture on the outcomes of attention assessments. The results of this pilot trial are expected to provide new insights on how Eastern and Western medicine can complement one another and improve the treatment of cognitive impairments in early stroke rehabilitation. Including patients with different cultural backgrounds allows a more generalisable interpretation of the results but also poses risks of performance bias. Using standardised and well-described assessments, validated for each region, is pivotal to allow pooling of the data. Clinical Trails.gov ID: NCT02324959 (8 December 2014)

Balance dysfunction after stroke limits patients’ general function and participation in daily life. Previous researches have suggested that Tai Chi exercise could offer a positive improvement in older individuals’ balance function and reduce the risk of falls. But convincing evidence for the effectiveness of enhancing balance function after stroke with Tai Chi exercise is still inadequate. Considering the difficulties for stroke patients to complete the whole exercise, the current trial evaluates the benefit of Tai Chi Yunshou exercise for patients with balance dysfunction after stroke through a cluster randomization, parallel-controlled design. A single-blind, cluster-randomized, parallel-controlled trial will be conducted. A total of 10 community health centers (5 per arm) will be selected and randomly allocated into Tai Chi Yunshou exercise group or balance rehabilitation training group. Each community health centers will be asked to enroll 25 eligible patients into the trial. 60 minutes per each session, 1 session per day, 5 times per week and the total training round is 12 weeks. Primary and secondary outcomes will be measured at baseline and 4-weeks, 8-weeks, 12-weeks, 6-week follow-up, 12-week follow-up after randomization. Safety and economic evaluation will also be assessed. This protocol aims to evaluate the effectiveness of Tai Chi Yunshou exercise for the balance function of patients after stroke. If the outcome is positive, this project will provide an appropriate and economic balance rehabilitation technology for community-based stroke patients. Chinese Clinical Trial Registry: ChiCTR-TRC-13003641. Registration date: 22 August, 2013 http://www.chictr.org/usercenter/project/listbycreater.aspx .

Background Post-stroke cognitive impairment (PSCI) lessens quality of life, restricts the rehabilitation of stroke, and increases the social and economic burden stroke imposes on patients and their families. Therefore effective treatment is of paramount importance. However, the treatment of PSCI is very limited. The primary aim of this protocol is to propose a lower cost and more effective therapy, and to confirm the long-term effectiveness of a therapeutic regimen of Traditional Chinese Medicine (TCM) rehabilitation for PSCI. Methods/Design A prospective, multicenter, large sample, randomized controlled trial will be conducted. A total of 416 eligible patients will be recruited from seven inpatient and outpatient stroke rehabilitation units and randomly allocated into a therapeutic regimen of TCM rehabilitation group or cognitive training (CT) control group. The intervention period of both groups will last 12 weeks (30 minutes per day, five days per week). Primary and secondary outcomes will be measured at baseline, 12 weeks (at the end of the intervention), and 36 weeks (after the 24-week follow-up period). Discussion This protocol presents an objective design of a multicenter, large sample, randomized controlled trial that aims to put forward a lower cost and more effective therapy, and confirm the long-term effectiveness of a therapeutic regimen of TCM rehabilitation for PSCI through subjective and objective assessments, as well as highlight its economic advantages. Trial registration This trial was registered with the Chinese Clinical Trial Registry (identifier: ChiCTR-TRC-14004872) on 23 June 2014. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0795-x) contains supplementary material, which is available to authorized users.

Objective. This study aimed to identify abnormal hippocampal functional connectivity (FC) following ischemic stroke using resting-state fMRI. We also explored whether abnormal hippocampal FC could be modulated by integrated cognitive therapy and tested whether these alterations were associated with cognitive performance.Methods. 18 right-handed cognitively impaired ischemic stroke patients and 18 healty control (HC) subjects were included in this study. Stroke subjects were scanned at baseline and after integrated cognitive therapy, while HCs were only scanned at baseline, to identify regions that show significant correlations with the seed region. Behavioral and cognitive assessments were obtained before each scan.Results. During the resting state, we found abnormal hippocampal FC associated with temporal regions, insular cortex, cerebellum, and prefrontal cortex in stroke patients compared to HCs. After integrated cognitive therapy, however, the stroke group showed increased hippocampal FC mainly located in the prefrontal gyrus and the default mode network (DMN). Altered hippocampal FC was associated with cognitive improvement.Conclusion. Resting-state fMRI may provide novel insight into the study of functional networks in the brain after stroke. Furthermore, altered hippocampal FC may be a compensatory mechanism for cognitive recovery after ischemic stroke.

Background Aphasia is a common and severely disabling complication in stroke patients. It usually brings about lower rates of functional recovery, longer rehabilitation length of stay (LOS), and significantly poorer LOS efficiency (LOS-Eff), resulting in higher rehabilitation costs compared to patients without aphasia. It also decreases the quality of life and increases the mortality of stroke patients. The evidence currently available suggests that the effect of acupuncture combined with language training for apoplectic aphasia is statistically better than speech and language therapy (SLT) alone, but there remains a lack of high-quality randomized controlled trials. Acupuncture combined with language training is relatively low-cost and especially suitable for community-based rehabilitation for aphasia patients after stroke, taking its medical and health facilities which are always deficient in manpower and material resources into account. The aim of the present study is to develop an effective standard therapeutic program for apoplectic aphasia in communities. Methods/Design In a randomized controlled clinical trial with blinded assessment, 290 eligible patients with aphasia due to stroke will be randomly allocated into a control group or an experimental group. The course of this trial will comprise a 4-week intervention and a 12-week follow-up period. Five assessment points, including baseline, 2 and 4 weeks after treatment, 6 and 12 weeks after follow-up, are set to dynamically observe the changes of curative effects. Primary outcome measures are the differences in the score on both the China rehabilitation research center aphasia examination (CRRCAE) and Boston diagnostic aphasia examination - Chinese version (BDAE-C) after intervention and follow-up. The Modified Barthel Index (MBI), 36-Item Short Form Health Survey (SF-36), and results of blood oxygen level dependent-functional magnetic resonance imaging (BOLD-fMRI) examination are considered as the secondary outcome measures. Other outcomes will include rate of adverse events and economic effects. Discussion If the outcome is positive, this project will offer a low-cost appropriate technology for community health centers (CHCs) in the rehabilitation of aphasia patients after stroke, and could be implemented on a large scale, both in China and worldwide. Trial registration Chinese Clinical Trial Registry: ChiCTR-TRC-13003703. Registration date: 18 October 2013.

Objective: This meta-analysis was conducted to evaluate the efficacy of acupuncture on cognitive impairment (function) after a stroke. Design: Randomized controlled trials (RCTs) comparing acupuncture with no acupuncture in addition to medicine or rehabilitation were identified from databases (PubMed, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, VIP Chinese Periodical Database, Wangfang Chinese Periodical Database, Chinese Bio-medicine Database, Cochrane Library, and Chinese medical literature databases) and two relevant journals (Chinese Acupuncture and Moxibustion and the Journal of Shanghai Acupuncture and Moxibustion). Meta-analyses were conducted for the eligible RCTs. Results: Twenty-one trials with a total of 1421 patients met inclusion criteria. Pooled random-effects estimates of the change in the Mini-Mental State Examination were calculated for the comparison of acupuncture with no acupuncture in addition to medicine or rehabilitation. Following 4 weeks and 8 weeks of intervention with acupuncture, the merged mean difference was 3.14 (95% confidence interval [CI], 2.06–4.21; p