Neurogranin as an important regulator in swimming training to improve the spatial memory dysfunction of mice with chronic cerebral hypoperfusion

Background:Vascular cognitive impairment caused by chronic cerebral hypoperfusion(CCH)has become a hot issue worldwide.Aerobic exercise positively contributes to the preservation or restoration of cognitive abilities;however,the specific mechanism has remained inconclusive.And recent studies found that neurogranin(Ng)is a potential biomarker for cognitive impairment.This study aims to investigate the underlying role of Ng in swimming training to improve cognitive impairment.Methods:To test this hypothesis,the clustered regularly interspaced short palindromic repeats(CRISPR)-associated protein 9(Cas9)system was utilized to construct a strain of Ng conditional knockout(Ng cKO)mice,and bilateral common carotid artery stenosis(BCAS)surgery was performed to prepare the model.In Experiment 1,2-month-old male and female transgenic mice were divided into a control group(wild-type littermate,n=9)and a Ng cKO group(n=9).Then,2-month-old male and female C57BL/6 mice were divided into a sham group(C57BL/6,n=12)and a BCAS group(n=12).In Experiment 2,2-month-old male and female mice were divided into a sham group(wild-type littermate,n=12),BCAS group(n=12),swim group(n=12),BCAS+Ng cKO group(n=12),and swim+Ng cKO group(n=12).Then,7 days after BCAS,mice were given swimming training for 5 weeks(1 week for adaptation and 4 weeks for training,5 days a week,60 min a day).After intervention,laser speckle was used to detect cerebral blood perfusion in the mice,and the T maze and Morris water maze were adopted to test their spatial memory.Furthermore,electrophysiology and Western blotting were conducted to record long-term potential and observe the expressions of Ca^(2+)pathway-related proteins,respectively.Immunohistochemistry was applied to analyze the expression of relevant markers in neuronal damage,inflammation,and white matter injury.Results:The figures showed that spatial memory impairment was detected in Ng cKO mice,and a sharp decline of cerebral blood flow and an impairment of progressive spatial memory were observed in BCAS mice.Regular swimming training improved the spatial memory impairment of BCAS mice.This was achieved by preventing long-term potential damage and reversing the decline of Ca^(2+)signal transduction pathway-related proteins.At the same time,the results suggested that swimming also led to improvements in neuronal death,inflammation,and white matter injury induced by CCH.Further study adopted the use of Ng cKO transgenic mice,and the results indicated that the positive effects of swimming training on cognitive impairments,synaptic plasticity,and related pathological changes caused by CCH could be abolished by the knockout of Ng.Conclusion:Swimming training can mediate the expression of Ng to enhance hippocampal synaptic plasticity and improve related pathological changes induced by CCH,thereby ameliorating the spatial memory impairment of vascular cognitive impairment.

Cortical activity in patients with high-functioning ischemic stroke during the Purdue Pegboard Test:insights into bimanual coordinated fine motor skills with functional near-infrared spectroscopy

After stroke,even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity,leading to reduced functional independence.Bilateral arm training has been proposed as a promising intervention to address these deficits.However,the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear,limiting the development of more targeted interventions.To address this gap,our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and coordination.Twenty-four high-functioning patients with ischemic stroke(7 women,17 men;mean age 64.75±10.84 years)participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test,which measures unimanual and bimanual finger and hand dexterity.We found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks,with bimanual tasks inducing higher cortical activation than the assembly subtask.Importantly,patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test subtasks.Notably,the observed neural response patterns varied depending on the specific subtask.In the unaffected hand task,the differences were primarily observed in the ipsilesional hemisphere.In contrast,the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task,respectively.While significant correlations were found between cortical activation and unimanual tasks,no significant correlations were observed with bimanual tasks.This study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke,highlighting task-dependent neural responses.The findings also suggest that patients who exhibit better bimanual performance demonstrate more efficient cortical activation.Therefore,incorporating bilateral arm training in post-stroke rehabilitation is important for better outcomes.The combination of functional near-infrared spectroscopy with functional motor paradigms is valuable for assessing skills and developing targeted interventions in stroke rehabilitation.

Regulation of extracellular signal-regulated kinase 1/2 influences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia

Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor （U0126） was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and KuT0 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac- celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/ reperfusion.

Protective effects of dl-3n-butylphthalide against diffuse brain injury

DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema.

Hemiplegia Patients Treatment Should Combine Acupuncture with Rehabilitation Treatment

The acupuncturetherapy for hemiplegiapatients is popular insome Asian countries,and it has been graduallyaccepted in the rehabili-tative medical field ofsome developed countries.Although numer-ous clinical and experimental studies have beendone,many doctors usu-

Profile of biological characterizations and clinical application of corneal stem/progenitor cells

Corneal stem/progenitor cells are typical adult stem/progenitor cells.The human cornea covers the front of the eyeball,which protects the eye from the outside environment while allowing vision.The location and function demand the cornea to maintain its transparency and to continuously renew its epithelial surface by replacing injured or aged cells through a rapid turnover process in which corneal stem/progenitor cells play an important role.Corneal stem/progenitor cells include mainly corneal epithelial stem cells,corneal endothelial cell progenitors and corneal stromal stem cells.Since the discovery of corneal epithelial stem cells(also known as limbal stem cells)in 1971,an increasing number of markers for corneal stem/progenitor cells have been proposed,but there is no consensus regarding the definitive markers for them.Therefore,the identification,isolation and cultivation of these cells remain challenging without a unified approach.In this review,we systematically introduce the profile of biological characterizations,such as anatomy,characteristics,isolation,cultivation and molecular markers,and clinical applications of the three categories of corneal stem/progenitor cells.

Potential Targets and Molecular Mechanism of Quercetin Against Knee Osteoarthritis

Objective The objective of this study was to clarify the potential mechanism of quercetin against knee osteoarthritis(KOA)based on network pharmacology and molecular docking.Methods The targets of quercetin were predicted by PubChem and Swiss Target Prediction databases,and the targets of KOA were obtained by DisGeNET,OMIM,and GeneCards databases.Then,the targets of quercetin and KOA were intersected to find the potential targets of quercetin against KOA.The protein–protein interaction network was constructed through the STRING database,and the core targets were screened.Gene ontology(GO)functions enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID database.The drug–target–pathway–disease network was constructed by Cytoscape software,and the molecular docking verification was performed by Vina.Results There were 49 potential targets for quercetin against KOA,including 10 core targets.GO functions enrichment analysis showed that the biological process of quercetin against KOA mainly involved the negative regulation of apoptotic process,collagen catabolic process,and extracellular matrix disassembly.KEGG pathway enrichment analysis showed that quercetin against KOA was closely related to PI3K-Akt signaling pathway,Rap 1 signaling pathway,FoxO signaling pathway,Ras signaling pathway,TNF signaling pathway,and ErbB signaling pathway.The results of molecular docking showed that the binding energies between ligand and receptors were less than−5 kcal·mol−1.Conclusions The molecular mechanism of quercetin against KOA involves many targets and pathways,which can regulate the proliferation and apoptosis of chondrocytes,degradation of extracellular matrix,and inflammatory reaction.Quercetin can stably bind to the active pockets of core target proteins,thereby exerting the effect against KOA.

Is effect of transcranial direct current stimulation on visuomotor coordination dependent on task difficulty?

Transcranial direct current stimulation （tDCS）, an emerging technique for non-invasive brain stimulation, is increasingly used to induce changes in cortical excitability and modulate motor behavior, especially for upper limbs. The purpose of this study was to investigate the effects of tDCS of the primary motor cortex on visuomotor coordination based on three levels of task difficulty in healthy subjects. Thirty-eight healthy participants underwent real tDCS or sham tDCS. Using a single-blind, sham-controlled crossover design, tDCS was applied to the primary motor cortex. For real tDCS conditions, tDCS intensity was 1 mA while stimulation was applied for 15 minutes. For the sham tDCS, electrodes were placed in the same position, but the stimu- lator was turned off after 5 seconds. Visuomotor tracking task, consisting of three levels （levels 1, 2, 3） of difficulty with higher level indicating greater difficulty, was performed before and after tDCS application. At level 2, real tDCS of the primary motor cortex improved the accurate index compared to the sham tDCS. However, at levels 1 and 3, the accurate index was not significantly increased after real tDCS compared to the sham tDCS. These findings suggest that tasks of mod- erate difficulty may improve visuomotor coordination in healthy subjects when tDCS is applied compared with easier or more difficult tasks.

Serum level changes of insulin-like growth factor-1 and amino acids in children with cerebral palsy following functional exercise plus head acupuncture therapy

BACKGROUND： In the past few years, there were many studies about the pathophysiology of insulin-like growth factor-1 （IGF-1）, as well as glutamic acid （GLU） and γ-aminobutyric acid （GABA） in hypoxic-ischemic brain damage （HIBD）. IGF-1 plays a protective role in brain damage. The over release of excitatory amino acids （EAA） plays an important role in acute neuronal death, which delays neuronal death. The disproportion of increasing of excitatory and inhibitory amino acids can cause different extent HIBD. However, there is rare report about the change of IGF-1 and neurotransmitter level in serum of cerebral palsy （CP） children. OBJECTIVE ： To observe the levels of serum IGF-1, GABA and GLU before and after functional exercise plus head acupuncture therapy and single functional exercise, then study the effective mechanism of IGF-1, GABA and GLU in the occurrence and development of CP, and compare those with normal control group. DESIGN： Case-control study SETTING： College of Rehabilitation Medicine, Jiamusi University, Prevention and Treatment Center of Child Cerebral Palsy in Heilongjiang Province. PARTICIPANTS： CP group： Sixty CP children came from Prevention and Treatment Center of Child Cerebra Palsy in Heilongjiang Province between April 2005 and March 2006 were selected in this study. All the cases were consistent with the diagnostic criteria and the type of cerebral palsy and finally diagnosed with CT and MRI examinations. There were 35 males and 25 females aged from 8 months to 4 years with the mean age o （2.0±0.5） years. And then, they were randomly divided into two groups. Twenty-six cases were received functional exercise, and the other 34 cases were treated with functional exercise and head acupuncture. Contro group： Thirty healthy children were from kindergarten and community for health examination in June 2005 There were 15 males and 15 females aged from 8 month to 4 years with the mean age of （2.0±0.5） years. AI guardians agreed with the participation of this experiment.METHODS ： （1） Bobath and Vojta treatment method were used for twice a day, thirty minutes for each time Treatment plans were different personally. Functional exercise plus head acupuncture group： Functional exercise was as the same as above. Head acupuncture treatment zone was adopted, 30# acupuncture needles, followed fur skin to stab （needle body and skin form 15°-30°）, pricked into aponeurosis of occipitofron talis muscle underlayer by means of 200 times per minute twisting needle body, lasted 3 minutes and stayed for 30 minutes. Needles were moved once every 10 minutes and manipulated intermittently. Certain quantity of stimulu., was kept once every other day. Fifteen days were regarded as a course, and patients were taken a rest of 3-7 days and received the second course. （2） Venous blood was collected on the next day of hospitalization and a 3 months after treatment, and venous blood in control group was collected at health examination. The lever o IGF-1 was measured by radio-immunity method. The lever of GABA and GLU were measured by high-performance liquid chromatography. （3）Specimen mean was compared with ttest and analysis of variance, t＇ tes was used in the one of heterogeneity of variance. MAIN OUTCOME MEASURES： The changes of serum IGF-1, GABA and G LU in CP children before and afte functional exercise plus head acupuncture therapy and single functional exercise therapy, and comparison., with normal control group. RESULTS： All 30 children in the control group and 60 CP children were involved in the final analysis （1） Befor（ treatment： The levels of IGF-1 and GABA were significantly lower than those in control group （t =28.885, P 〈 0.01, t＇= -46.530, P 〈 0.05）; whereas the levels of GLU were significantly higher than those in control group （t＇=35.282, P 〈 0.05）. （2） After treatment： The levels of serum IGF-1 and GLU were （32.36±12.92） μg/L an（ （37.47±11.28） mmol/L in functional exercise group, respectively; meanwhile, the levels of them were （38.17± 13.84） μg/L and （41.91±11.78） mmol/L in functional exercise plus head acupuncture group, respectively. Bott of them in the two groups were lower than those in the control group [（74.90±7.18） μg/L, （92.99±4.52） mmol/L t ＇= -13.543 to -23.504, P 〈 0.05]; however, the level of GLU was higher than that in the control group [（141.25±17.14）, （133.03±21.78） mmol/L, t＇=17.534, 13.765, P〈 0.05]. The level of serum GLU was lower after treatment than before treatment in both functional exercise group and functional exercise plus hea（ acupuncture group [（154.17±13.00）, （152.97±15.34） mmol/L, t =3.064, 4.364, P 〈 0.05]. In addition, the level of IGF-1 and GABA were higher after treatment than before treatment [（23.03±9.51）, （22.16±7.81） μg/L （28.72±8.91）, （28.02±8.58） mmol/L, t =2.964-5.874, P〈 0.05]. CONCLUSION ： （1） IGF-1, GLU and GABA may participate in the pathophysiological course of cerebral palsy （2）Both functional exercise combining head acupuncture therapy and single functional exercise therapy are good for the recovery of cerebral injury, and the former may be even better for it.

The Feasibility of a Novel Dual-Task Exercise Program Which Integrates Balance, Gaze, Mobility and Cognition in Community Dwelling Older Adults: Protocol for a Randomized Clinical Pilot Trial

Background: Mobility limitations and cognitive impairments which are common with ageing often coexist, causing a reduction in the levels of physical and mental activity and are prognostic of future adverse health events and falls. Consequently, multi-task training paradigms that simultaneously address both mobility and cognition benefit healthy ageing are important to consider in rehabilitation as well as primary prevention. Objectives: An exploratory RCT is being conducted to: a) describe the feasibility and acceptability of the study design and process, procedures, resources and management in two game-based dual-task training programs delivered in the community;b) to explore the lived experiences of the study participants who completed their respective exercise programs. A secondary objective is to obtain preliminary data on the therapeutic effectiveness of the two dual-task training programs. Methods: Thirty healthy older community dwelling participants aged 70 - 85 with previous history of falls will be recruited and randomized to either dual- task treadmill walking (experimental group) or dual-task recumbent bicycle (control group). Data analysis: The qualitative data will be analyzed by two investigators using a content analysis approach. For the quantitative data, outcome measures will be collected pre and post intervention and included measures to assess core balance, spatial-temporal gait variables, visual tracking and cognitive function, as well as, balance and gait analysis under dual-task conditions. Discussion: This research will demonstrate the feasibility of the dual-task training programs in the community, and demonstrate the system’s ability to improve targeted and integrated (dual-task) aspects of balance, mobility, gaze, and cognitive performance. A blended analysis of balance, mobility gaze and cognition will also contribute to a better understanding of the functional consequences of decline in physical and mental skills with age. Trial registration: This pilot clinical trial has been registered at ClinicalTrials.gov Protocol Registration System: NCT01940055.

Does hemispheric lateralization influence therapeutic effects of transcranial direct current stimulation?

This study investigated the effect of transcranial direct current stimulation（t DCS） polarity depending on lateralized function of task property in normal individuals performing visuomotor and simple repetitive tasks. Thirty healthy participants with no neurological disorders were recruited to participate in this study. Participants were randomly allocated into active or control condition. For the active condition, t DCS intensity was 2 m A with stimulation applied for 15 minutes to the right hemisphere（t DCS condition）. For the sham control, electrodes were placed in the same position, but the stimulator was turned off after 30 seconds（sham condition）. The tapping and tracking task tests were performed before and after for both conditions. Univariate analysis revealed significant difference only in the tracking task. For direct comparison of both tasks within each group, the tracking task had significantly higher Z score than the tapping task in the t DCS group（P 〈 0.05）. Thus, our study indicates that stimulation of the right hemisphere using t DCS can effectively improve visuomotor（tracking） task over simple repetitive（tapping） task.

The Extension Rate of the Medial Collateral Ligament of the Knee Joint during the Valgus Stress Test: Two Case Reports

This study aimed to evaluate the influence of measuring the length of the medial collateral ligament (MCL) to compare the MCL burden when the knee joint is placed under valgus stress in the open and closed and closed kinetic chain. Two examiners conducted the examination. The MCL length was measured using ultrasonography. Two subjects were measured in unload bearing and load-bearing positions, with and without valgus stress test at the knee joint extension and 30° flexion, under eight different measurement conditions. The MCL of the subject was delineated in the longitudinal direction using an ultrasound system. The attachment points of the medial femoral and tibial condyle of the MCL were identified, and the ligament length was measured. The MCL rate before and after the valgus stress test in the loading and unloading positions was calculated. The MCL length increased by an average of 8.9% when the external stress test was performed in the non-weight bearing and knee extension positions and by an average of 17.0% when external stress was applied in the non-weight bearing and knee flexion positions. The MCL length increased by an average of 12.2% when the external stress test was performed in the load-bearing and knee extension positions and an average of 8.9% when the valgus stress test was applied in load-bearing and knee flexion positions. In conclusion, the effect of valgus stress on the MCL differs between load-bearing and non-load-bearing positions. It is considered that the dynamic stabilization mechanism works in the knee joint flexion position in the load position and works simultaneously as the static stabilization mechanism, which limits the knee joint valgus and reduces the extension rate of MCL. Therefore, this study reconsiders the shifting of traditional therapy from open kinetic chain to close kinetic chain.

Contents of myelin-basic protein and S-100 in serum and brain tissue of neonatal rats with intrauterine infection-caused brain injury

BACKGROUND： The change of the content of myelin basic protein （MBP） in serum and brain tissue is the biochemical diadynamic index of amyelination. S-100 is a specific and sensitive marker of central nervous system （CNS） injury. Whether or not the content of S-100 and MBP in blood and brain tissue can be used as the quantitative index for early diagnosing the intrauterine infection-caused brain injury still needs investigation. OBJECTIVE ： To observe whether or not MBP and S-100 detection can be used as the biochemical indexes for early diagnosing the intrauterine infection-caused brain injury. DESIGN： Randomized controlled animal experiment. SETTING ： Laboratory of Pediatric Neuro-rehabilitation, Medical College of Rehabilitation, Jiamusi University. MATERIALS ： Sixty female and thirty male common Wistar rats, weighing from 180 to 240 g, were provided by the Experimental Animal Center of Jiamusi University. Reagent： Lipopolysacchande（LPS, serological type 055： B5, SIGMA Company of USA）; MBP enzyme linked immunosobent assay （ELISA） immunoreagent kit （Preclinical Recombination DNA Laboratory, Chengdu Huaxi Medical Center, Sichuan Province）; S-100 ELISA immunoreagent kit （ Department of Physiology, the Fourth Military Medical University of Chinese PLA） and bovine serum albumin（Haitaike Biotechnology Co.,Ltd.）. METHODS ： This experiment was carried out in the Laboratory of Pediatric Neuro-Rehabilitation, Experimental Animal Center, Department of Pathology and Central Laboratory of Jiamusi University from July 2005 to March 2006. ① Preparation of models and grouping： The female and male rats were placed in one cage at 2： 1 at 17：00 o＇clock. Vaginal smear was checked at 8：00 on the next morning. Sperm was found and 0 day of pregnancy was recorded. Pregnant rats were bred in another cage. The pregnant 47 rats were randomly divided into 2 groups： control group （n =10） and experimental group （n =37）. The experimental pregnant rats were intraperitoneally injected with LPS 500 μg/kg per day at embryonic 18 days in following 2 days. As controls, 10 pregnant rats were intraperitoneally injected with the same dose of normal saline at the same time. ②After delivery, mother rats in both groups were sacrificed, and then the infection status of uterus and placenta was observed through haematoxylin and eosin （HE） staining. A great quantity of neutrophilic leukocytes infiltrated, which was the identification standard. Twenty control neonatal rats and 20 experimental neonatal rats （7 days） were selected randomly. The changes of ultrastructure in cortex, hippocamp, internal capsule and callus were detected under an electron microscope, and MBP and S-100 in serum and brain tissues were detected by ELiSA method.③ t test was used for comparing the differences of measurement data. MAIN OUTCOME MEASURES ： ① The content of MBP and S-100 in serum and brain tissue of neonatal rats between two groups. ② Pathological detection results of uterus and placenta of neonatal rats.③ Detection results of brain tissue under an electron microscope. RESULTS： Forty-seven pregnant rats and forty neonatal rats were involved in the result analysis. ① The content of MBP in serum and brain tissue of neonatal rats： MBP content in brain tissue of neonatal rats in the experimental group was significantly lower than that in the control group [（5.898±1.050） μg/L vs. （7.006±1.071） μg/L, t =3.221, P 〈 0.01], while MBP content in the serum of neonatal rats in the experimental group was significantly higher than that in the control group[（3.912±0.783） μg/L vs. （2.625±0.766） μg/L, t =5.120, P 〈 0.01]. ②The content of S-100 in serum and brain tissue of neonatal rats： The content of S-100 in brain tissue and serum of neonatal rats in the experimental group was significantly higher than that in the control group, respectively, [（6.412±0.820） μg/L vs. （5.377±0.712） μg/L; （3.393±0.550） μg/L vs. （2.298±0.614）μg/L,t=4.154, 5.791, P 〈 0.01]. ③ Pathological detection results of uterus and placenta of neonatal rats： Uterine wall and placenta of pregnant rats were found with vascular engorgement and edema, and a great quantity of neutrophilic leukocyte infiltrated. Meanwhile, there was not evident inflammatory reaction in the pregnant rats in the control group. Detection of brain tissue of neonatal rats under an electron microscope： Obvious brain injury was found in the neonatal rats of the experimental rats, but was not found in the control group. CONCLUSION ： LPS successfully causes intrauterine infection of pregnant rats, and the neonatal rats born by which have obvious brain injury. Through detecting the changes of the content of MBP and S-100 on these animal models, it is concluded that MBP and S-100 can be used as the indexes to early diagnose brain injury, and they are the sensitive biochemical indexes to reflect the extent of early brain injury.

Electroacupuncture activates AMPKα1 to improve learning and memory in the APP/PS1 mouse model of early Alzheimer’s disease by regulating hippocampal mitochondrial dynamics

Objective Studies have shown that electroacupuncture(EA)can alleviate cognitive impairments from Alzheimer’s disease(AD)by regulating the expression of adenosine monophosphate-activated protein kinase(AMPK),but the specific mechanism involved remains to be elucidated.Therefore,this study explores the potential mechanism by which EA improves cognitive function from the perspective of mitochondrial dynamics.Methods The four-month-old transgenic mice with amyloid precursor protein(APP)/presenilin 1(PS1)and AMPKα1-subunit conditional knockout(AMPKα1-cKO)were used for experiments.To evaluate the effects of EA treatment on cognitive function,the T-maze and Morris water maze were used.In addition,chemical exchange saturation transfer,thioflavin staining,transmission electron microscopy,mitochondrial membrane potential,and Western blotting were used to examine the potential mechanisms underlying the effects of EA on APP/PS1 mice.Results Both APP/PS1 mice and AMPKα1-cKO mice exhibited dysfunction in mitochondrial dynamics accompanied by learning and memory impairment.Inactivation of the AMPK/peroxisome proliferator-activated receptor-γcoactivator-1α(PGC-1α)pathway increased pathological amyloid-β(Aβ)deposition and aggravated the dysfunction in mitochondrial dynamics.In addition,EA rescued learning and memory deficits in APP/PS1 mice by activating the AMPK/PGC-1αpathway,specifically by reducing pathological Aβdeposition,normalizing energy metabolism,protecting the structure and function of mitochondria,increasing the levels of mitochondrial fusion proteins,and downregulating the expression of fission proteins.However,the therapeutic effect of EA on cognition in APP/PS1 mice was hindered by AMPKα1 knockout.Conclusion The regulation of hippocampal mitochondrial dynamics and reduction in Aβdeposition via the AMPK/PGC-1αpathway are critical for the ability of EA to ameliorate cognitive impairment in APP/PS1 mice.

Is transcranial direct current stimulation a potential method for improving response inhibition?

Inhibitory control of movement in motor learning requires the ability to suppress an inappropriate action, a skill needed to stop a planned or ongoing motor response in response to changes in a variety of environments. This study used a stop-signal task to determine whether transcranial direct-current stimulation over the pre-supplementary motor area alters the reaction time in motor inhibition. Forty healthy subjects were recruited for this study and were randomly assigned to either the transcranial direct-current stimulation condition or a sham-transcranial direct-current stimulation condition. All subjects consecutively performed the stop-signal task before, during, and after the delivery of anodal transcranial direct-current stimulation over the pre-supplementary motor area （pre-transcranial direct-current stimulation phase, transcranial direct-current stimulation phase, and post-transcranial direct-current stimulation phase）. Compared to the sham condition, there were significant reductions in the stop-signal processing times during and after transcranial direct-current stimulation, and change times were significantly greater in the transcranial direct-current stimulation condition. There was no significant change in go processing-times during or after transcranial direct-current stimulation in either condition. Anodal transcranial direct-current stimulation was feasibly coupled to an interactive improvement in inhibitory control. This coupling led to a decrease in the stop-signal process time required for the appropriate responses between motor execution and inhibition. However, there was no transcranial direct-current stimulation effect on the no-signal reaction time during the stop-signal task. Transcranial direct-current stimulation can adjust certain behaviors, and it could be a useful clinical intervention for patients who have difficulties with response inhibition.

Exercise-induced muscle fatigue in the unaffected knee joint and its influence on postural control and lower limb kinematics in stroke patients

This study aimed to investigate the effects of exercise-induced muscle fatigue in the unaffected knee joint on postural control and kinematic changes in stroke patients. Forty participants（20 stroke patients, 20 age-matched healthy participants） were recruited. To induce fatigue, maximum voluntary isometric contractions were performed in the unaffected knee joint in a Leg Extension Rehab exercise machine using the pneumatic resistance. We measured static and dynamic balance and lower-limb kinematics during gait. Changes in postural control parameters anteroposterior sway speed and total center of pressure distance differed significantly between the stroke and control groups. In addition, changes in gait kinematic parameters knee and ankle angles of initial contact differed significantly between stroke（paretic and non-paretic） and control groups. Muscle fatigue in the unaffected knee and ankle impaired postural control and debilitates kinematic movement of ipsilateral and contralateral lower limbs, and may place the fatigued stroke patients at greater risk for falls.

Apolipoprotein E mimetic peptide protects against diffuse brain injury

Apolipoprotein E plays a crucial role in inhibiting chronic neurodegenerative processes. Howev-er, its impact on neurological function following diffuse brain injury is still unclear. This study was designed to evaluate the therapeutic effects and mechanisms of action of apolipoprotein E mimetic peptide on diffuse brain injury. Apolipoprotein E mimetic peptide was administered into the caudal vein of rats with diffuse brain injury before and after injury. We found that apo-lipoprotein E mimetic peptide signiifcantly decreased the number of apoptotic neurons, reduced extracellular signal-regulated kinase1/2 phosphorylation, down-regulated Bax and cytochrome c expression, decreased malondialdehyde content, and increased superoxide dismutase activity in a dose-dependent manner. These experimental ifndings demonstrate that apolipoprotein E mimetic peptide improves learning and memory function and protects against diffuse brain injury-induced apoptosis by inhibiting the extracellular signal-regulated kinase1/2-Bax mito-chondrial apoptotic pathway.

Chinese Tuina remodels the synaptic structure in neuropathic pain rats by downregulating the expression of N-methyl D-aspartate receptor subtype 2B and postsynaptic density protein-95 in the spinal cord dorsal horn

OBJECTIVE:To investigate whether the Chinese massage system,Tuina,exerts analgesic effects in a rat model of chronic constriction injury(CCI)by remodeling the synaptic structure in the spinal cord dorsal horn(SCDH).METHODS:Sixty-nine male Sprague–Dawley rats were randomly and evenly divided into the normal group,sham group,CCI group,CCI+Tuina group,CCI+MK-801[an N-methyl D-aspartate receptor subtype 2B(NR2B)antagonist]group,and CCI+MK-801+Tuina group.The neuropathic pain model was established using CCI with right sciatic nerve ligation.Tuina was administered 4 d after CCI surgery,using pressing manipulation for 10 min,once daily.Motor function was observed with the inclined plate test,and pain behaviors were observed by the Von Frey test and acetone spray test.At 19 d after surgery,the L3-L5 spinal cord segments were removed.Glutamate,interleukin 1β(IL-1β),and tumor necrosis factor-α(TNF-α)levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of NR2B and postsynaptic density protein-95(PSD-95)were detected by Western blot,and the synaptic structure was observed by transmission electron microscopy(TEM).RESULTS:CCI reduced motor function and caused mechanical and cold allodynia in rats,increased glutamate concentration and TNF-αand IL-1βlevels,and increased expression of synapse-related proteins NR2B and PSD-95 in the SCDH.TEM revealed that the synaptic structure of SCDH neurons was altered.Most of these disease-induced changes were reversed by Tuina and intrathecal injection of MK-801(P<0.05 or<0.01).For the majority of experiments,no significant differences were found between the CCI+MK-801 and CCI+MK-801+Tuina groups.CONCLUSIONS:Chinese Tuina can alleviate pain by remodeling the synaptic structure,and NR2B and PSD-95 receptors in the SCDH may be among its targets.

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

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

Abnormal Metabolic Connectivity in Rats at the Acute Stage of Ischemic Stroke

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 18F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemi- sphere, and increased metabolism mainly in the contrale- sional 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 con- nectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.