Neural differentiation of human Wharton's jelly-derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats

Human Wharton’s jelly-derived mesenchymal stem cells(h WJ-MSCs)have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.     

Resuscitating acupuncture therapy for glucose metabolism in acute cerebral infarction of basal ganglia

BACKGROUND: Acupuncture can improve motor function in patients with cerebral infarction, and activate brain glucose metabolism in relevant brain areas. However, the association between encephalic region activation and acupuncture, as well as the clinical significance of activationremain unclear.OBJECTIVE: Through the use of positron emission tomography-computed tomography (PET-CT), acute cerebral infarction patients were analyzed for global cerebral metabolism, cerebral infarction focus, peripheral edema, and pyramidal tract pathway changes, which were directly related to clinical symptoms. The influence of resuscitating acupuncture on cerebral glucose metabolism was analyzed in patients with acute cerebral infarction in basal ganglia.DESIGN, TIME AND SETTING: Randomized, controlled, clinical trials were performed from March 2007 to October 2008 at the PET-CT Center of the General Hospital of Tianjin Medical University,China.PARTICIPANTS: Twelve patients with acute basal ganglia infarction were recruited from the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, -lianjin Chinese Medicine Hospital, and Affiliated Hospital of Medical College of Chinese People's Armed Police Force.METHODS: The cerebral infarcted patients were randomly assigned to acupuncture and control groups. In addition to routine treatment, the acupuncture group was treated by acupuncture at the main acupoints for resuscitation [Neiguan (PC 6), Renzhong (DU 26), and Sanyinjiao (SP 6)], while the control group received routine treatment.MAIN OUTCOME MEASURES: Before and after treatment, patients with acute cerebral infarction were evaluated for global brain, cerebral infarction focus, and surrounding edema and glucose metabolism in encephalic region of pyramidal tract conduction by 18-labeled fluorodeoxyglucose for PET-CT imaging.RESULTS: The resuscitating acupuncture therapy can significantly activate the metabolism of global brain, infarction center and surrounding edema in patients with cerebral infarction in basal ganglia, also has effects on the activation of glucose metabolism in the encephalic regions of pyramidal tract pathway (P < 0.05).CONCLUSION: Resuscitating acupuncture was superior to routine treatment for significantly activating glucose metabolism in patients with acute cerebral basal ganglia infarction.     

Speech and language therapy for aphasia following subacute stroke

The aim of this study was to investigate the time window, duration and intensity of optimal speech and language therapy applied to aphasic patients with subacute stroke in our hospital. The study consisted of 33 patients being hospitalized for stroke rehabilitation in our hospital with first stroke but without previous history of speech and language therapy. Sixteen sessions of impairment-based speech and language therapy were applied to the patients, 30–60 minutes per day, 2 days a week, for 8 successive weeks. Aphasia assessment in stroke patients was performed with Gülhane Aphasia Test-2 before and after treatment. Compared with before treatment, fluency of speech, listening comprehension, reading comprehension, oral motor evaluation, automatic speech, repetition and naming were improved after treatment. This suggests that 16 seesions of speech and language therapy, 30–60 minutes per day, 2 days a week, for 8 successive weeks, are effective in the treatment of aphasic patients with subacute stroke.     

Mechanisms of electroacupuncture effects on acute cerebral ischemia/reperfusion injur y:possible association with upregulation of transforming growth factor beta 1

Electroacupuncture at the head acupoints Baihui(GV20) and Shuigou(GV26) improves recovery of neurological function following ischemic cerebrovascular events,but its mechanism remains incompletely understood.We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1(TGF-β1).To test this,we established a rat model of cerebral ischemia by middle cerebral artery occlusion.Electroacupuncture was performed at Baihui and Shuigou with a dispersedense wave at an alternating frequency of 2 and 150 Hz,and at a constant intensity of 3 m A.Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days.Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment.Furthermore,serum level of TGF-β1 was greater after electroacupuncture than after no treatment.Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury,and exerts neuroprotective effects.     

Constraint-induced movement therapy in treatment of acute and sub-acute stroke: a meta-analysis of 16 randomized controlled trials

OBJECTIVE: The aim of this meta-analysis was to evaluate the clinical efficacy of constraint-induced movement therapy in acute and sub-acute stroke.DATA SOURCES: The key words were stroke, cerebrovascular accident, constraint-induced therapy, forced use, and randomized controlled trial. The databases, including China National Knowledge Infrastructure, Wan Fang, Weipu Information Resources System, Chinese Biomedical Literature Database, Pub Med, Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, were searched for studies on randomized controlled trials for treating acute or sub-acute stroke published before March 2016. DATA SELECTION: We retrieved relevant randomized controlled trials that compared constraint-induced movement therapy in treatment of acute or sub-acute stroke with traditional rehabilitation therapy(traditional occupational therapy). Patients were older than 18 years, had disease courses less than 6 months, and were evaluated with at least one upper extremity function scale. Study quality was evaluated, and data that met the criteria were extracted. Stata 11.0 software was used for the meta-analysis. OUTCOME MEASURES: Fugl-Meyer motor assessment of the arm, the action research-arm test, a motor activity log for amount of use and quality of movement, the Wolf motor function test, and a modified Barthel index.RESULTS: A total of 16 prospective randomized controlled trials(379 patients in the constraint-induced movement-therapy group and 359 in the control group) met inclusion criteria. Analysis showed significant mean differences in favor of constraint-induced movement therapy for the Fugl–Meyer motor assessment of the arm(weighted mean difference(WMD) = 10.822; 95% confidence intervals(95% CI): 7.419–14.226), the action research-arm test(WMD = 10.718; 95% CI: 5.704–15.733), the motor activity log for amount of use and quality of movement(WMD = 0.812; 95% CI: 0.331–1.293) and the modified Barthel index(WMD = 10.706; 95% CI: 4.417–16.966). CONCLUSION: Constraint-induced movement therapy may be more beneficial than traditional rehabilitation therapy for improving upper limb function after acute or sub-acute stroke.     

Changes in brain functional network connectivity after stroke简

Studies have shown that functional network connection models can be used to study brain net- work changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlat- ed to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea- lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke.     

Analgesic effects of balanced acupuncture versus body acupuncture in low-back and leg pain patients with lumbar disc herniation, as assessed by resting-state functional magnetic resonance imaging

Balanced acupuncture, a single-acupoint balance therapy, regulates the balance of the cerebral center, and is characterized by exerting quick effects and a short treatment course. A total of 20 low-back and leg pain patients with lumbar disc herniation were treated with balanced acupuncture or body acupuncture. Central mechanisms of varied acupunctures were compared using resting-state functional MRI. Patients from both groups received functional MRI before and after acupuncture. Functional connectivity in brain regions that were strongly associated with the bilateral amygdala was analyzed utilizing AFNI software. Visual analogue scale scores were greater in the balanced acupuncture group compared with the body acupuncture group. Function of the endogenous pain regulation network was enhanced in patients in the balanced acupuncture group, but was not changed in the body acupuncture group. This result indicates that the analgesic effects of body acupuncture do not work through the central nervous system. These data suggest that balanced acupuncture exerts analgesic effects on low-back and leg pain patients with lumbar disc herniation by regulating the function of the endogenous pain regulation network.     

Mechanism of Kinect-based virtual reality training for motor functional recovery of upper limbs after subacute stroke

The Kinect-based virtual reality system for the Xbox 360 enables users to control and interact with the game console without the need to touch a game controller, and provides rehabilitation training for stroke patients with lower limb dysfunctions. However, the underlying mechanism remains un- clear. In this study, 18 healthy subjects and five patients after subacute stroke were included. The five patients were scanned using functional MRI prior to training, 3 weeks after training and at a 12-week follow-up, and then compared with healthy subjects. The FugI-Meyer Assessment and Wolf Motor Function Test scores of the hemiplegic upper limbs of stroke patients were significantly increased 3 weeks after training and at the 12-week follow-up. Functional MRI results showed that contralateral primary sensorimotor cortex was activated after Kinect-based virtual reality training in the stroke patients compared with the healthy subjects. Contralateral primary sensorimotor cortex, the bilateral supplementary motor area and the ipsilateral cerebellum were also activated during hand-clenching in all 18 healthy subjects. Our findings indicate that Kinect-based virtual reality training could promote the recovery of upper limb motor function in subacute stroke patients, and brain reorganization by Kinect-based virtual reality training may be linked to the contralateral sen- sorimotor cortex.     

Efficacy of suspended moxibustion in stroke rats is associated with a change in tail temperature

Suspended moxibustion-produced heat can transfer from the acupoint to other sites of the body. The suspended moxibustion should be terminated when clinical propagated sensation disappears, because this implies that the quantity of moxibustion is sufficient. We wanted to investigate if this phenomenon also occurs in experimental animals. In the present study, a rat model of stroke was established and treated with suspended moxibustion at Dazhui (DU14) for 60 minutes. Results showed that the increase in tail temperature began at 15 minutes after suspended moxibustion and decreased gradually at 40 minutes. In addition, neurological function was significantly improved in stroke rats with tail temperature increase following suspended moxibustion, and this effect was associated with significantly reduced tumor necrosis factor α and interleukin 1β mRNA. However, there was no significant difference between 40-and 60-minute suspended moxibustion. The findings indicate that elevated tail temperature began to decrease at 40 minutes after suspended moxibustion, and further suspended moxibustion was not useful in the recovery of stroke rats.     

Verbascoside promotes the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra

Tyrosine hydroxylase is a key enzyme in dopamine biosynthesis. Change in tyrosine hydroxylase expression in the nigrostriatal system is closely related to the occurrence and development of Parkinson’s disease. Verbascoside, an extract from Radix Rehmanniae Praeparata has been shown to be clinically effective in treating Parkinson’s disease. However, the underlying mechanisms remain unclear. It is hypothesized that the effects of verbascoside on Parkinson’s disease are related to tyrosine hydroxylase expression change in the nigrostriatal system. Rat models of Parkinson’s disease were established and verbascoside (60 mg/kg) was administered intraperitoneally once a day. After 6 weeks of verbascoside treatment, rat rotational behavior was alleviated; tyrosine hydroxylase mRNA and protein expression and the number of tyrosine hydroxylase-immunoreactive neurons in the rat right substantia nigra were signiifcantly higher than the Parkinson’s model group. These ifndings suggest that the mechanism by which verbascoside treats Parkinson’s disease is related to the regeneration of tyrosine hy-droxylase-immunoreactive neurons in the substantia nigra.     

Low frequency repetitive transcranial magnetic stimulation improves motor dysfunction after cerebral infarction

Low frequency(≤ 1 Hz) repetitive transcranial magnetic stimulation(r TMS) can affect the excitability of the cerebral cortex and synaptic plasticity. Although this is a common method for clinical treatment of cerebral infarction, whether it promotes the recovery of motor function remains controversial. Twenty patients with cerebral infarction combined with hemiparalysis were equally and randomly divided into a low frequency r TMS group and a control group. The patients in the low frequency r TMS group were given 1-Hz r TMS to the contralateral primary motor cortex with a stimulus intensity of 90% motor threshold, 30 minutes/day. The patients in the control group were given sham stimulation. After 14 days of treatment, clinical function scores(National Institute of Health Stroke Scale, Barthel Index, and Fugl-Meyer Assessment) improved significantly in the low frequency r TMS group, and the effects were better than that in the control group. We conclude that low frequency(1 Hz) r TMS for 14 days can help improve motor function after cerebral infarction.     

Needling at the Waiguan (SJ5) in healthy limbs deactivated functional brain areas in ischemic stroke patients A functional magnetic resonance imaging study

Deactivation is common in cerebral functional imaging. However, the physiological mechanisms responsible for this phenomenon remain poorly understood. The present study analyzed 12 ischemic stroke patients, who were randomly assigned to two groups: one group underwent sham needling and true needling at the Waiguan (SJ 5) in the healthy upper limb and the other group underwent sham and true needling at a sham point. Functional magnetic resonance imaging results showed no activation points in brain tissues fo...     

Functional magnetic resonance imaging evaluation of brain function reorganization in cerebral stroke patients after constraint-induced movement therapy

In this study, stroke patients received constraint-induced movement therapy for 3 weeks. Before and after constraint-induced movement therapy, the flexibility of their upper limbs on the affected side was assessed using the Wolf motor function test, and daily use of their affected limbs was assessed using the movement activities log, and cerebral functional reorganization was assessed by functional magnetic resonance imaging. The Wolf motor function test score and the movement activities log quantity and quality scores were significantly increased, while action performance time in the Wolf motor function test was significantly decreased after constraint-induced movement therapy. By functional magnetic resonance imaging examination, only scattered activation points were visible on the affected side before therapy. In contrast, the volume of the activated area was increased after therapy. The activation volume in the sensorimotor area was significantly different before and after therapy, and the activation area increased and appeared adjusted. In addition to the activated area around the lesions being decreased, there were also some new activated areas, including the supplementary movement area, premotor area and the ipsilateral sensorimotor area. Our findings indicate that constraint-induced movement therapy significantly improves the movement ability and daily use of the affected upper limbs in stroke patients and promotes cerebral functional reorganization.     

Virtual reality training improves balance function

Virtual reality is a new technology that simulates a three-dimensional virtual world on a com- puter and enables the generation of visual, audio, and haptic feedback for the full immersion of users. Users can interact with and observe objects in three-dimensional visual space without limitation. At present, virtual reality training has been widely used in rehabilitation therapy for balance dysfunction. This paper summarizes related articles and other articles suggesting that virtual reality training can improve balance dysfunction in patients after neurological diseases. When patients perform virtual reality training, the prefrontal, parietal cortical areas and other motor cortical networks are activated. These activations may be involved in the reconstruction of neurons in the cerebral cortex. Growing evidence from clinical studies reveals that virtual reality training improves the neurological function of patients with spinal cord injury, cerebral palsy and other neurological impairments. These findings suggest that virtual reality training can acti- vate the cerebral cortex and improve the spatial orientation capacity of patients, thus facilitating the cortex to control balance and increase motion function.     

Cerebral mechanism of puncturing at He-Mu point combination for functional dyspepsia:study protocol for a randomized controlled parallel trial

Acupuncture is widely used to treat functional dyspepsia with satisfactory outcomes. Combination of the He and Mu acupoints is commonly used and has a synergistic effect on functional dyspepsia;however, its underlying mechanisms remain unclear.Therefore, a ran-domized controlled parallel clinical trial is currently underway at Chengdu University of Traditional Chinese Medicine, China.This trial is designed to explore the efficacy of and central responses to the He-Mu point combination in patients with functional dyspepsia using functional magnetic resonance imaging. A total of 105 patients with functional dyspepsia will be allocated into 3 groups:the low-He point group (puncturing at Zusanli (ST36)), Mu point group (puncturing at Zhongwan (CV12)), and He-Mu point combination group (puncturing at ST36 and CV12). Every participant will receive 20 sessions of manual acupuncture for 4 weeks.The needles will be inserted perpen-dicularly to a depth of 1 to 2 cun.The angle of rotation and twisting will range from 90 to 180 degrees, while lifting and thrusting will range from 0.3 to 0.5 cm.The various manipulations will be performed 60 to 90 times per minute.The needles will remain in place for 30 minutes, during which manipulation will be applied every 10 minutes. Magnetic resonance imaging will be performed before and after 20 sessions of acupuncture.The primary outcome is symptom improvement according to the Chinese version of the Nepean Dyspepsia Index. Secondary outcomes include the Leeds dyspepsia questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Beck Anxiety Inventory, Beck Depression Inventory, and visual analogue scale scores before and after 10 and 20 sessions of acupuncture. Needle sensa-tion and adverse events will be used to assess the therapeutic effects.This study will promote more widespread awareness of the benefits of acupoint combination in the clinical setting and provide a further explanation of the neuromechanism by which acupuncture at the He-Mu point combination for functional dyspepsia. Registration:Chinese Clinical Trial Registry, ChiCTR-IOR-15006402.     

Acupuncture at Waiguan （SJ5） and sham points influences activation of functional brain areas of ischemic stroke patients： a functional magnetic resonance imaging study

Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group （true acupuncture at right Waiguan （SJ5）） and sham point group （sham acupuncture）. Results of functional magnetic resonance imaging revealed activation in right parietal lobe （Brodmann areas 7 and 19）, the right temporal lobe （Brodmann area 39）, the right limbic lobe （Brodmann area 23） and bilateral oc-cipital lobes （Brodmann area 18）. Furthermore, inhibition of bilateral frontal lobes （Brodmann area 4, 6, and 45）, right parietal lobe （Brodmann areas 1 and 5） and left temporal lobe （Brodmann area 21 ） were observed in the true point group. Activation in the precuneus of right parietal lobe （Brodmann area 7） and inhibition of the left superior frontal gyrus （Brodmann area 10） was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex （Brodmann area 5） is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.     

Acupuncture at Baihui and Dazhui reduces brain cell apoptosis in heroin readdicts简

Acupuncture at Baihui （GV20） and Dazhui （GV14） reduces neuronal loss and attenuates ultra- structural damage in cerebral ischemic rats. However, whether acupuncture can treat addiction and prevent readdiction through changes to brain cell ultrastructure remains unknown. In this study, cell apoptosis was observed in the hippocampus and frontal lobe of heroin readdicted rats by electron microscopy. Immunohistochemical staining displayed a reduction in Bcl-2 ex- pression and an increase in Bax expression in the hippocampus and frontal lobe. After rats were given acupuncture at Baihui and Dazhui, the pathological damage in the hippocampus and frontal lobe was significantly reduced, Bcl-2 expression was upregulated and Bax expression was downregulated. Acupuncture exerted a similar effect with methadone, a commonly used drug for clinical treatment of drug addiction. Experimental findings suggest that acupuncture at Dazhui and Baihui can prevent brain cell apoptosis in heroin readdicted rats.     

Ursolic acid induces neural regeneration after sciatic nerve injury

In this study,we aimed to explore the role of ursolic acid in the neural regeneration of the injured sciatic nerve.BALB/c mice were used to establish models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis at 0.5 cm below the ischial tuberosity.The successfully generated model mice were treated with 10,5,or 2.5 mg/kg ursolic acid via intraperitoneal injection.Enzyme-linked immunosorbent assay results showed that serum S100 protein expression level gradually increased at 1-4 weeks after sciatic nerve injury,and significantly decreased at 8 weeks.As such,ursolic acid has the capacity to significantly increase S100 protein expression levels.Real-time quantitative PCR showed that S100 mRNA expression in the L4-6 segments on the injury side was increased after ursolic acid treatment.In addition,the muscular mass index in the soleus muscle was also increased in mice treated with ursolic acid.Toluidine blue staining revealed that the quantity and average diameter of myelinated nerve fibers in the injured sciatic nerve were significantly increased after treatment with ursolic acid.10 and 5 mg/kg of ursolic acid produced stronger effects than 2.5 mg/kg of ursolic acid.Our findings indicate that ursolic acid can dose-dependently increase S100 expression and promote neural regeneration in BALB/c mice following sciatic nerve injury.     

Hippocampal gene expression in a rat model of depression after electroacupuncture at the Baihui and Yintang acupoints简

Preliminary basic research and clinical findings have demonstrated that electroacupuncture ther- apy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level; there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we profiled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depres- sion-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui （DU20） and Yintang （EX-HN3） regulates the expression of 21 genes. Real-time PCR showed that the genes Vgf, lgf2, Trnp32, Loc500373, Hifla, Folrl, Nrnb, and Rtn were upregulated or downregulated in depression and that their expression tended to nor- malize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes.