After-effects of repetitive transcranial magnetic stimulation with parameter dependence on long-term potentiation-like plasticity and object recognition memory in rats.

Objective: To investigate the after-effects of 25-Hz repetitive transcranial magnetic stimulation (rTMS) at 60, 100, and 120% resting motor threshold (rMT) on long-term potentiation (LTP) in the rat hippocampus, to clarify the intensity dependence of rTMS, and to determine whether it simultaneously affects learning and memory ability. Methods: Five rats were randomly selected from 70 male Wistar rats, and evoked rMT potentials were recorded in response to magnetic stimulation. The remaining 65 rats were randomly assigned to five groups (n = 13), including sham rTMS, 1 Hz 100% rMT, and 25 Hz rTMS groups with 3 subgroups of 60% rMT, 100% rMT, and 120% rMT. Five rats in each group were anesthetized and induced by a priming TMS-test design for population spike (PS) response of the perforant path-dentate gyrus in the hippocampus; the remaining eight rats in each group were evaluated for object recognition memory in the novel object recognition (NOR) task after the different rTMS protocols. Results: Forty-five percent (approximately 1.03 T) of the magnetic stimulator output was confirmed as rMT in the biceps femoris muscle. The PS ratio was ranked as follows: 25 Hz 100% rMT (267.78 ± 25.71%) > sham rTMS (182 ± 9.4%) >1 Hz 100% rMT (102.69 ± 6.64%) > 25 Hz 120% rMT (98 ± 11.3%) > 25 Hz 60% rMT (36 ± 8.5%). Significant differences were observed between the groups, except for the difference between the 25 Hz 120% rMT and the 1 Hz 100% rMT groups (p = 0.446). LTP was successfully induced over the 60-min recording period only in the sham rTMS and 25 Hz 100% rMT groups. Moreover, these two groups spent more time exploring a novel object than a familiar object during the NOR task (p < 0.001), suggesting long-term recognition memory retention. In the between-group analysis of the discrimination index, the following ranking was observed: 25 Hz 100% rMT (0.812 ± 0.158) > sham rTMS (0.653 ± 0.111) > 25 Hz 120% rMT (0.583 ± 0.216) >1 Hz 100% rMT (0.581 ± 0.145) > 25 Hz 60% rMT (0.532 ± 0.220). Conclusion: The after-effect of 25-Hz rTMS was dependent on stimulus intensity and provided an inverted (V-shaped) bidirectional modulation on hippocampal plasticity that involved two forms of metaplasticity. Furthermore, the effects on the recognition memory ability were positively correlated with those on LTP induction in the hippocampus in vivo.

The Effects of APP-Based Intervention for Depression Among Community-Dwelling Individuals With Spinal Cord Injury: A Randomized Controlled Trial.

OBJECTIVE: To assess the effect of a self-management intervention delivered by mobile application (APP) for depression among community-dwelling individuals with spinal cord injury (SCI). DESIGN: Randomized controlled trial. SETTINGS: General communities in China. PARTICIPANTS: Community-dwelling individuals with SCI who were diagnosed within 2 years were recruited in this study (N=98). It was a convenience sample with an average age of 41.71, 82.7% participants were men. INTERVENTIONS: Participants in the intervention group (n=49) received 5 sessions on self-management training provided by nurse-led multidisciplinary team via APP at the second, fourth, sixth, eighth, and 12th weeks, respectively, after they discharge from hospitals. Participants in the control group (n=49) received routine telephone counselling provided by follow-up nurses at the 12th week after they discharge. OUTCOME MEASURE: The outcome of this study is depression, which is not the primary outcomes in the registration of this program. Depression was measured by version 2 of Beck Depression Inventory at discharge (T0), the 12th week after discharge from hospitals (T1), and the 24th week after discharge from hospitals (T2). RESULTS: There were 98 participants (49 in the intervention group and 49 in the control group) completing the intervention and data collection. Compared with the control group, the intervention group had lower level of depression at T2 (B=-5.76; 95% CI=-9.97, -1.54; P=.007). Small to moderate effect sizes on depression favoring the intervention were demonstrated at T1 (Cohen's d=-.178) and T2 (Cohen's d=-.535). CONCLUSIONS: APP-based self-management support can be a potential intervention to reduce depression among community-dwelling individuals with SCI.

Long-Term Motor Cortical Electrical Stimulation Ameliorates 6-Hydroxydopamine-Induced Motor Dysfunctions and Exerts Neuroprotective Effects in a Rat Model of Parkinson's Disease.

OBJECTIVE: Cortical electrical stimulation (CES) can modulate cortical excitability through a plasticity-like mechanism and is considered to have therapeutic potentials in Parkinson's disease (PD). However, the precise therapeutic value of such approach for PD remains unclear. Accordingly, we adopted a PD rat model to determine the therapeutic effects of CES. The current study was thus designed to identify the therapeutic potential of CES in PD rats. METHODS: A hemiparkinsonian rat model, in which lesions were induced using unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle, was applied to identify the therapeutic effects of long-term (4-week) CES with intermittent theta-burst stimulation (iTBS) protocol (starting 24 h after PD lesion observation, 1 session/day, 5 days/week) on motor function and neuroprotection. After the CES intervention, detailed functional behavioral tests including gait analysis, akinesia, open-field locomotor activity, apomorphine-induced rotation as well as degeneration level of dopaminergic neurons were performed weekly up to postlesion week 4. RESULTS: After the CES treatment, we found that the 4-week CES intervention ameliorated the motor deficits in gait pattern, akinesia, locomotor activity, and apomorphine-induced rotation. Immunohistochemistry and tyrosine hydroxylase staining analysis demonstrated that the number of dopamine neurons was significantly greater in the CES intervention group than in the sham treatment group. CONCLUSION: This study suggests that early and long-term CES intervention could reduce the aggravation of motor dysfunction and exert neuroprotective effects in a rat model of PD. Further, this preclinical model of CES may increase the scope for the potential use of CES and serve as a link between animal and PD human studies to further identify the therapeutic mechanism of CES for PD or other neurological disorders.

Cross-cultural and psychometric property assessment of the Moorong Self-Efficacy Scale in Chinese patients with spinal cord injury.

PURPOSE: To translate the Moorong Self-Efficacy Scale (MSES) into Chinese and to examine its reliability and validity in patients with spinal cord injury (SCI). METHODS: A cross-sectional study design was employed. The MSES was translated into Chinese by forward- and back-translation and its psychometric properties were examined among 176 patients with SCI recruited from four rehabilitation centers in China using convenience sampling. RESULTS: In this study, all 176 patients were aged from 18 to 90 years old with an average of 39.51 ± 14.07. The content validity index of the scale was 0.99. Principal components analysis with varimax orthogonal rotation was used. Three factors were extracted accounting for 39.083%, 11.149%, and 8.391% of the total variance and labeled as general self-efficacy (eight items), social self-efficacy (five items), and self-management self-efficacy (three items). Confirmatory factor analysis showed acceptable fit compared with previous studies. Pearson's correlation coefficient between the total scores of the MSES and the General Self-Efficacy Scale was 0.660 (p < 0.001). Cronbach's α coefficient was 0.892 for total items and 0.862, 0.817, and 0.739 for the three factors. The interclass correlation coefficients between the pretest and retest were 0.859 (0.733-0.925) for the total score. CONCLUSIONS: The Chinese version of the MSES is reliable and valid, suggesting that it is suitable for evaluating self-efficacy of Chinese patients with SCI.Implications for rehabilitationThe satisfactory reliability and validity of the Chinese version of the Moorong Self-Efficacy Scale (MSES) confirmed its suitability as a tool to measure self-efficacy among Chinese patients with spinal cord injury (SCI).The Chinese version of the MSES could be used to reflect the important and specific aspects of self-efficacy in patients with SCI such as self-care, social interaction, and daily activities, and to help medical stuff giving more targeted intervention.

Asymmetric cortical activation in healthy and hemiplegic individuals during walking: A functional near-infrared spectroscopy neuroimaging study.

Background: This study investigated the cortical activation mechanism underlying locomotor control during healthy and hemiplegic walking. Methods: A total of eight healthy individuals with right leg dominance (male patients, 75%; mean age, 40.06 ± 4.53 years) and six post-stroke patients with right hemiplegia (male patients, 86%; mean age, 44.41 ± 7.23 years; disease course, 5.21 ± 2.63 months) completed a walking task at a treadmill speed of 2 km/h and a functional electrical stimulation (FES)-assisted walking task, respectively. Functional near-infrared spectroscopy (fNIRS) was used to detect hemodynamic changes in neuronal activity in the bilateral sensorimotor cortex (SMC), supplementary motor area (SMA), and premotor cortex (PMC). Results: fNIRS cortical mapping showed more SMC-PMC-SMA locomotor network activation during hemiplegic walking than during healthy gait. Furthermore, more SMA and PMC activation in the affected hemisphere was observed during the FES-assisted hemiplegic walking task than during the non-FES-assisted task. The laterality index indicated asymmetric cortical activation during hemiplegic gait, with relatively greater activation in the unaffected (right) hemisphere during hemiplegic gait than during healthy walking. During hemiplegic walking, the SMC and SMA were predominantly activated in the unaffected hemisphere, whereas the PMC was predominantly activated in the affected hemisphere. No significant differences in the laterality index were noted between the other groups and regions (p > 0.05). Conclusion: An important feature of asymmetric cortical activation was found in patients with post-stroke during the walking process, which was the recruitment of more SMC-SMA-PMC activation than in healthy individuals. Interestingly, there was no significant lateralized activation during hemiplegic walking with FES assistance, which would seem to indicate that FES may help hemiplegic walking recover the balance in cortical activation. These results, which are worth verifying through additional research, suggest that FES used as a potential therapeutic strategy may play an important role in motor recovery after stroke.

Cortical Electrical Stimulation Ameliorates Traumatic Brain Injury-Induced Sensorimotor and Cognitive Deficits in Rats.

Objective: Individuals with different severities of traumatic brain injury (TBI) often suffer long-lasting motor, sensory, neurological, or cognitive disturbances. To date, no neuromodulation-based therapies have been used to manage the functional deficits associated with TBI. Cortical electrical stimulation (CES) has been increasingly developed for modulating brain plasticity and is considered to have therapeutic potential in TBI. However, the therapeutic value of such a technique for TBI is still unclear. Accordingly, an animal model of this disease would be helpful for mechanistic insight into using CES as a novel treatment approach in TBI. The current study aims to apply a novel CES scheme with a theta-burst stimulation (TBS) protocol to identify the therapeutic potential of CES in a weight drop-induced rat model of TBI. Methods: TBI rats were divided into the sham CES treatment group and CES treatment group. Following early and long-term CES intervention (starting 24 h after TBI, 1 session/day, 5 days/week) in awake TBI animals for a total of 4 weeks, the effects of CES on the modified neurological severity score (mNSS), sensorimotor and cognitive behaviors and neuroinflammatory changes were identified. Results: We found that the 4-week CES intervention significantly alleviated the TBI-induced neurological, sensorimotor, and cognitive deficits in locomotor activity, sensory and recognition memory. Immunohistochemically, we found that CES mitigated the glial fibrillary acidic protein (GFAP) activation in the hippocampus. Conclusion: These findings suggest that CES has significant benefits in alleviating TBI-related symptoms and represents a promising treatment for TBI.

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.

Effects of App-Based Transitional Care on the Self-Efficacy and Quality of Life of Patients With Spinal Cord Injury in China: Randomized Controlled Trial.

BACKGROUND: Spinal cord injury (SCI) severely impairs the physical and mental health of patients, decreasing their self-efficacy in coping with daily life and quality of life (QOL). In China, a large gap remains between the complex long-term health needs of SCI patients and the current community care system. With the prevalence of mobile terminals, the usage of mobile health apps has the potential to fill this gap by extending qualified medical resources to the families of SCI patients. Our team developed the app Together for the transitional care of home-dwelling SCI patients in China. OBJECTIVE: This study aimed to evaluate the effects of app-based transitional care on the self-efficacy and QOL of SCI patients. METHODS: Through a three-round Delphi process, an Android app was designed. Both medical staff and patients could access the app. Medical staff used it for providing remote transitional care to SCI patients. Patients used it to view transitional care time and send messages to medical staff. Thereafter, a multicenter and assessor-blinded randomized controlled trial was conducted. Participants (n=98) who had SCI and lived at home following discharge were recruited and randomly assigned to a study group (n=49) and control group (n=49) using a randomized number list in four research centers. Patients in both groups received systematic discharge education before discharge. The study group received five follow-ups conducted by trained nurses through the app, which had four core functions, namely remote assessment, health education, interdisciplinary referral, and patient interaction, at weeks 2, 4, 6, 8, and 12 following discharge. The control group received a routine telephone follow-up conducted by nurses at week 12 following discharge. The outcome measures were the Moorong Self-Efficacy Scale (MSES) and 36-item Short-Form Health Survey (SF-36) scores. Data were collected before discharge (T0) and at weeks 12 (T1) and 24 following discharge (T2). Differences between the groups were tested by repeated measures analysis of variance and simple effect analysis. RESULTS: After the follow-up, the total MSES scores in the study group improved over time (T0=67.80, T1=71.90, and T2=76.29) and were higher than those in the control group (T2=64.49) at 24 weeks following discharge (simple effect analysis: F1=8.506, P=.004). Regarding the total SF-36 score, although it was higher in patients from the study group (T2=65.36) than those from the control group (T2=58.77) at 24 weeks following discharge, only time effects were significant (F2,95=6.671, P=.002) and neither the group effects nor the interaction effects influenced the change in QOL (group effects: F1,96=0.082, P=.78; interaction effects: F2,95=3.059, P=.052). CONCLUSIONS: This study confirmed that app-based transitional care improves the self-efficacy of SCI patients. Nevertheless, QOL improvement is not yet evident. Future investigations with larger sample sizes and longer observation periods are warranted to further verify the effects. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IPR-17012317; http://www.chictr.org.cn/showproj.aspx?proj=19828.

Translation and validation of the Chinese version of the Spinal Cord Independence Measure (SCIM III) Self-Report.

STUDY DESIGN: A cross-sectional psychometric study. OBJECTIVE: To translate, culturally adapt and validate the Chinese version of the Spinal Cord Independence Measure III-Self Report (SCIM-SR). SETTING: Four rehabilitation centers in Guangzhou, Chengdu, and Shiyan, China. METHODS: Translation and cultural adaptation of the Chinese version of the SCIM-SR was conducted according to Brislin guidelines. A total of 147 spinal cord injury patients self-rated their functional independence using translated instrument. The psychometric properties of content validity, criterion-related validity, internal consistency reliability, and test-retest reliability were examined. RESULTS: The content validity index of the new scale was 0.99. The intraclass correlation coefficient between the total SCIM-SR and SCIM III scores was 0.935, and the coefficients for its three subscales were 0.899, 0.760, and 0.942. Bland-Altman analysis showed that the mean difference between the total SCIM-SR and SCIM III scores was 2.35 (95% confidence interval -0.58 to 5.28), and differences for the three subscales were 0.75 (-0.51-2.01), 1.30 (-0.63-3.23), and 0.30 (-0.80-1.40). The Cronbach's α coefficients for the total scale, the self-care subscale, and the mobility subscale were 0.908, 0.913, and 0.895, respectively. The α for the respiration and sphincter management subscale was 0.581. Test-retest reliability after 2 weeks yielded a Spearman coefficient for the total scale of and subscale values all above 0.73. CONCLUSIONS: Our results indicate acceptable validity and reliability of the Chinese version of SCIM-SR. It may facilitate long-term evaluations of independence in Chinese spinal cord injury patients in the community and at home.

Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats.

Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson's disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.

Using a Mobile App-Based International Classification of Functioning, Disability, and Health Set to Assess the Functioning of Spinal Cord Injury Patients: Rasch Analysis.

BACKGROUND: The International Classification of Functioning, Disability, and Health (ICF) is a unified system of functioning terminology that has been used to develop electronic health records and assessment instruments. Its application has been limited, however, by its complex terminology, numerous categories, uncertain operationalization, and the training required to use it well. Together is a mobile health app designed to extend medical support to the families of spinal cord injury (SCI) patients in China. The app's core framework is a set of only 31 ICF categories. The app also provides rating guidelines and automatically transforms routine assessment results to the terms of the ICF qualifiers. OBJECTIVE: The goal of the research is to examine the suitability of the ICF set used in the app Together for use as an instrument for assessing the functioning of SCI patients. METHODS: A cross-sectional study was conducted including 112 SCI patients recruited before discharge from four rehabilitation centers in China between May 2018 and October 2019. Nurses used the app to assess patient functioning in face-to-face interviews. The resulting data were then subjected to Rasch analysis. RESULTS: After deleting two categories (family relationships and socializing) and one personal factor (knowledge about spinal cord injury) that did not fit the Rasch model, the body functions and body structures, activities and participation, and contextual factors components of the ICF exhibited adequate fit to the Rasch model. All three demonstrated acceptable person separation indices. The 28 categories retained in the set were free of differential item functioning by gender, age, education level, or etiology. CONCLUSIONS: Together overcomes some of the obstacles to practical application of the ICF. The app is a reliable assessment tool for assessing functioning after spinal cord injury.

Outcome indicators in the transitional care of people with spinal cord injury in China: a Delphi survey based on the International Classification of Functioning, Disability and Health.

Objective: To identify the categories of the International Classification of Functioning, Disability and Health most suitable as outcome indicators in the transitional care for people with spinal cord injury in China.Methods: A three-round Delphi survey was conducted surveying 37 experts selected through purposive sampling. In the first round, each expert was required to suggest the most useful indicators in the transitional care for spinal cord injury patients. Categories of the International Classification of Functioning, Disability and Health were linked with the concepts extracted from the responses. In the second round, the experts were asked to make a yes/no judgment about the utility of those categories as outcome indicators and to rate their importance from 1 to 10. In the third round, the experts were asked to re-judge and re-rate the importance considering the second-round results.Results: Forty-one categories, seven personal factors, and three concepts not covered in the International Classification of Functioning, Disability and Health were identified. They generated agreement percentages over 80% in the third round. The means of the importance ratings ranged from 5.15 to 9.52.Conclusions: A set of categories and concepts was identified in the Delphi survey based on the International Classification of Functioning, Disability and Health. They provided a reference and a basis for establishing a system of outcome indicators in the transitional care for patients with spinal cord injury in China.Implications for rehabilitationIn China, the people with spinal cord injury who live at home after discharge urgently need professional transitional care which can be extended from medical institutions to families.The categories and concepts identified by the Delphi survey based on the International Classification of Functioning, Disability and Health reflect the focuses in the transitional care of people with spinal cord injury in China.Those categories and concepts provide a reference and a basis for establishing a system of outcome indicators in the transitional care for patients with spinal cord injury in China.

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).

Neuromodulatory Effects of Transcranial Direct Current Stimulation on Motor Excitability in Rats.

Transcranial direct current stimulation (tDCS) is a noninvasive technique for modulating neural plasticity and is considered to have therapeutic potential in neurological disorders. For the purpose of translational neuroscience research, a suitable animal model can be ideal for providing a stable condition for identifying mechanisms that can help to explore therapeutic strategies. Here, we developed a tDCS protocol for modulating motor excitability in anesthetized rats. To examine the responses of tDCS-elicited plasticity, the motor evoked potential (MEP) and MEP input-output (IO) curve elicited by epidural motor cortical electrical stimulus were evaluated at baseline and after 30 min of anodal tDCS or cathodal tDCS. Furthermore, a paired-pulse cortical electrical stimulus was applied to assess changes in the inhibitory network by measuring long-interval intracortical inhibition (LICI) before and after tDCS. In the results, analogous to those observed in humans, the present study demonstrates long-term potentiation- (LTP-) and long-term depression- (LTD-) like plasticity can be induced by tDCS protocol in anesthetized rats. We found that the MEPs were significantly enhanced immediately after anodal tDCS at 0.1 mA and 0.8 mA and remained enhanced for 30 min. Similarly, MEPs were suppressed immediately after cathodal tDCS at 0.8 mA and lasted for 30 min. No effect was noted on the MEP magnitude under sham tDCS stimulation. Furthermore, the IO curve slope was elevated following anodal tDCS and presented a trend toward diminished slope after cathodal tDCS. No significant differences in the LICI ratio of pre- to post-tDCS were observed. These results indicated that developed tDCS schemes can produce consistent, rapid, and controllable electrophysiological changes in corticomotor excitability in rats. This newly developed tDCS animal model could be useful to further explore mechanical insights and may serve as a translational platform bridging human and animal studies, establishing new therapeutic strategies for neurological disorders.

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

OBJECTIVE: To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. DATA SOURCES: PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. METHODS: Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. RESULTS: A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I2 = 71%, P = 0.0005). CONCLUSION: Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

Exercise improves recognition memory and synaptic plasticity in the prefrontal cortex for rats modelling vascular dementia.

OBJECTIVES: Functional electrical stimulation (FES) may induce involuntary exercise and make beneficial effects on vascular dementia (VD) by strengthening the BDNF-pCREB-mediated pathway and hippocampal plasticity. Whether FES improves recognition memory and synaptic plasticity in the prefrontal cortex (PFC) was investigated by establishing a VD model. METHODS: The VD rats were administered with two weeks of voluntary exercise, forced exercise, or involuntary exercise induced with FES. Sham-operated and control groups were also included. The behavioral changes were assessed with the novel object recognition test and novel object location test. The expression levels of key proteins related to synaptic plasticity in the PFC were also detected. RESULTS: All types of exercise improved the rats' novel object recognition index, but only voluntary exercise and involuntary exercise induced with FES improved the novel object location index. Any sort of exercise enhanced the expression of key proteins in the PFC. CONCLUSION: Involuntary exercise induced with FES can improve recognition memory in VD better than forced exercise. The mechanism is associated with increased synaptic plasticity in the PFC. FES may be a useful alternative tool for cognitive rehabilitation.

Effect of lamotrigine on seizure development in a rat pentylenetetrazole kindling model.

INTRODUCTION: Epileptogenesis is a process of seizure development. Lamotrigine is a novel antiepileptic drug which is also used for antiepileptogenic research. Kindling models are recommended as potentially useful tools for antiepileptogenic treatment discovery. However, previous studies demonstrated that the antiepileptogenic effect of lamotrigine is controversial in the electrical kindling model. Chemical kindling such as with pentylenetetrazole is another kindling model. The aims of this study were to examine whether lamotrigine could prevent the development of seizure in pentylenetetrazole kindling rats. METHODS: Female rats were kindled by subconvulsive doses of pentylenetetrazole (35 mg/kg) once every other day for 15 times. Thereafter, the kindled rats received different doses of lamotrigine (5, 10 and 20 mg/kg) before pentylenetetrazole to observe the anticonvulsant effect. For the antiepileptogenic experiment, rats were kindled as the same way while pretreated (1 h) with different doses of lamotrigine (5, 10 and 20 mg/kg) before each injection of pentylenetetrazole. After a washout period for 1 week, the rats were administrated with pentylenetetrazole again for 3 times. The seizures were recorded each time. Later it was in vivo electrophysiological experiments followed with histologic analysis. RESULTS: For the anticonvulsant experiment lamotrigine dose-dependently suppressed pentylenetetrazole-induced seizures. Here, 20 mg/kg of lamotrigine pretreatment significantly blocked the seizure development in rats for their seizure stages remained longer in 1-3 during the kindling phase. Mean seizure stages or generalized seizure durations in the 10 and 20 mg/kg lamotrigine pretreated groups were significantly lower or shorter when received 3 times of pentylenetetrazole after the washout period. Electrophysiological study also demonstrated 20 mg/kg of lamotrigine pretreatment obviously eliminated increased population spike amplitude in hippocampus. However, different doses of lamotrigine pretreatment could not alleviate severity of hippocampal neuronal damage. CONCLUSIONS: The results suggest that adequate doses of lamotrigine can prevent seizure development in the pentylenetetrazole kindling rat model.

Involuntary, Forced and Voluntary Exercises Equally Attenuate Neurocognitive Deficits in Vascular Dementia by the BDNF-pCREB Mediated Pathway.

A rat model of vascular dementia was used to compare the effects of involuntary exercise induced by functional electrical stimulation (FES), forced exercise and voluntary exercise on the recovery of cognitive function recovery and its underlying mechanisms. In an involuntary exercise (I-EX) group, FES was used to induce involuntary gait-like running on ladder at 12 m/min. A forced exercise group (F-EX) and a voluntary exercise group (V-EX) exercised by wheel running. The Barnes maze was used for behavioral assessment. Brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element binding protein (CREB) positive cells in hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were evaluated using immunohistochemical methods. Western blotting was used to assess the levels of BDNF, phosphorylated protein kinase B (Akt), tropomyosin receptor kinase B (TrkB), mitogen-activated protein kinase 1 and 2 (MEK1/2), ERK1/2 and CREB in BDNF-pCREB signaling in the hippocampus and prefrontal cortex. Involuntary, forced and voluntary exercises were all found to reverse the cognitive deficits of vascular dementia with about equal effectiveness. The number of BDNF, pCREB and pERK1/2 immunopositive cells was significantly increased in the hippocampal CA1, CA2/3 and DG regions in all three exercise groups. In addition, involuntary exercise activated BDNF and the phosphorylation of Akt, TrkB, MEK1/2, ERK1/2 and CREB in the hippocampus and prefrontal cortex equally as well as voluntary or forced exercise. These results suggest that involuntary exercise induced by FES may be as beneficial for alleviating cognitive deficits after cerebral ischemia.

Involuntary, forced and voluntary exercises are equally capable of inducing hippocampal plasticity and the recovery of cognitive function after stroke.

OBJECTIVES: Forced and voluntary exercises are known to improve cognition and induce neuroprotection after stroke, however, any effects of involuntary movement induced by functional electrical stimulation (FES) are unclear. The effects of involuntary exercise induced by FES, forced and voluntary exercise on the recovery of cognitive function in vascular dementia and the regional repair of ischaemic lesions were investigated using a rat model. METHODS: Wistar rats were randomly assigned to a sham group, a vascular dementia control group (VD), an involuntary exercise group (I-Ex), a forced exercise group (F-Ex) or a voluntary exercise group (V-Ex). An object recognition test (ORT) and an object location test (OLT) were used to evaluate the recovery of cognitive function. Levels of synapsin I (SYN), synaptophysin (SYP), postsynaptic density 95 (PSD-95), microtubule-associated protein 2 (MAP-2) and Tau in the hippocampus were evaluated using western blotting and immunohistochemistry. Nissl staining was applied to visualise the loss of viable neurons from the hippocampus. RESULTS: Involuntary exercise and voluntary exercise both improved cognition in terms of ORT and OLT results. Forced exercise only improved ORT results. The levels of SYN, PSD-95, MAP-2 and Tau in the hippocampus were enhanced by all three patterns of exercise training. Moreover, all three patterns reduced losses of dendrons and neurons in the hippocampal CA1 and CA2 zones, but without significant differences among the three exercise regimens. CONCLUSION: Involuntary exercise induced by FES has beneficial effects on cognitive function after vascular dementia comparable to those of forced and voluntary exercise.

The effectiveness of functional electrical stimulation based on a normal gait pattern on subjects with early stroke: a randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of four-channel FES based on a normal gait pattern on improving functional ability in subjects early after ischemic stroke. METHODS: Forty-five subjects were randomly assigned into a four-channel FES group (n=16), a placebo group (n=15), or a dual-channel group (n=14). Stimulation lasted for 30 min in each session with 1 session/day, 5 days a week for 3 weeks. All subjects were assessed at baseline, at 3 weeks of treatment, and at 3 months after the treatment had finished. The assessments included Fugl-Meyer Assessment (FMA), the Postural Assessment Scale for Stroke Patients (PASS), Berg Balance Scale (BBS), Functional Ambulation Category (FAC), and the Modified Barthel Index (MBI). RESULTS: All 3 groups demonstrated significant improvements in all outcome measurements from pre- to posttreatment and further gains at followup. The score of FMA and MBI improved significantly in the four-channel group at the end of the 3 weeks of training. And the scores of PASS, BBS, MBI, and FAC in the four-channel group were significantly higher than those of the placebo group. CONCLUSIONS: This study indicated that four-channel FES can improve motor function, balance, walking ability, and performance of activities of daily living in subjects with early ischemic stroke.