Il1r2 and Tnfrsf12a in transcranial magnetic stimulation effect of ischemic stroke via bioinformatics analysis.

Ischemic stroke refers to ischemic necrosis or softening of localized brain tissue. Transcranial magnetic stimulation (TMS) is a painless, noninvasive and green treatment method, which acts on the central nervous system through a pulsed magnetic field to assist in the treatment of central nervous system injury diseases. However, the role of Il1r2 and Tnfrsf12a in this is unknown. The ischemic stroke datasets GSE81302 and TMS datasets GSE230148 were downloaded from Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. The construction and analysis of protein-protein interaction (PPI) network and functional enrichment analysis were performed. Draw heat map gene expression. Through the Comparative Toxicogenomics Database (CTD) to find the most relevant and core gene diseases. TargetScan was used to screen miRNAs regulating DEGs. A total of 39 DEGs were identified. According to gene ontology (GO) analysis results, in biological process (BP) analysis, they were mainly enriched in the positive regulation of apoptosis process, inflammatory response, positive regulation of p38MAPK cascade, and regulation of cell cycle. In cellular component (CC) analysis, they were mainly enriched in the cell surface, cytoplasm, and extracellular space. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, they were mainly enriched in nf-κB signaling pathway, fluid shear stress and atherosclerosis, P53 signaling pathway, TNF signaling pathway, and apoptosis. Among the enrichment items of metascape, negative regulation of T cell activation, hematopoietic cell lineage, positive regulation of apoptotic process, fluid shear stress and atherosclerosis were observed in GO enrichment items. Five core genes (Socs3, Irf1, Il1r2, Ccr1, and Tnfrsf12a) were obtained, which were highly expressed in ischemic stroke samples. Il1r2 and Tnfrsf12a were lowly expressed in TMS samples. CTD analysis found that the core gene (Socs3, Irf1 and Il1r2, Ccr1, Tnfrsf12a) and ischemic stroke, atherosclerosis, hypertension, hyperlipidemia, thrombosis, stroke, myocardial ischemia, myocardial infarction, and inflammation. Il1r2 and Tnfrsf12a are highly expressed in ischemic stroke, but lowly expressed in TMS samples.

Lesion-specific cortical activation following sensory stimulation in patients with subacute stroke.

BACKGROUND: Sensory stimulation can play a fundamental role in the activation of the primary sensorimotor cortex (S1-M1), which can promote motor learning and M1 plasticity in stroke patients. However, studies have focused mainly on investigating the influence of brain lesion profiles on the activation patterns of S1-M1 during motor tasks instead of sensory tasks. Therefore, the objective of this study is to explore the lesion-specific activation patterns due to different brain lesion profiles and types during focal vibration (FV). METHODS: In total 52 subacute stroke patients were recruited in this clinical experiment, including patients with basal ganglia hemorrhage/ischemia, brainstem ischemia, other subcortical ischemia, cortical ischemia, and mixed cortical-subcortical ischemia. Electroencephalograms (EEG) were recorded following a resting state lasting for 4 min and three sessions of FV. FV was applied over the muscle belly of the affected limb's biceps for 3 min each session. Beta motor-related EEG power desynchronization overlying S1-M1 was used to indicate the activation of S1-M1, while the laterality coefficient (LC) of the activation of S1-M1 was used to assess the interhemispheric asymmetry of brain activation. RESULTS: (1) Regarding brain lesion profiles, FV could lead to the significant activation of bilateral S1-M1 in patients with basal ganglia ischemia and other subcortical ischemia. The activation of ipsilesional S1-M1 in patients with brainstem ischemia was higher than that in patients with cortical ischemia. No activation of S1-M1 was observed in patients with lesions involving cortical regions. (2) Regarding brain lesion types, FV could induce the activation of bilateral S1-M1 in patients with basal ganglia hemorrhage, which was significantly higher than that in patients with basal ganglia ischemia. Additionally, LC showed no significant correlation with the modified Barthel index (MBI) in all patients, but a positive correlation with MBI in patients with basal ganglia lesions. CONCLUSIONS: These results reveal that sensory stimulation can induce lesion-specific activation patterns of S1-M1. This indicates FV could be applied in a personalized manner based on the lesion-specific activation of S1-M1 in stroke patients with different lesion profiles and types. Our study may contribute to a better understanding of the underlying mechanisms of cortical reorganization.

Higher expression of PLEK and LY86 as the potential biomarker of carotid atherosclerosis.

Carotid atherosclerosis (AS) occurs in atherosclerotic lesions of the carotid artery, which can lead to transient ischemic attack and stroke in severe cases. However, the relationship between pleckstrin (PLEK) and lymphocyte antigen 86 (LY86) and carotid AS remains unclear. The carotid AS datasets GSE43292 and GSE125771 were downloaded from the gene expression omnibus database. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis was performed. Construction and analysis of protein-protein interaction network. Functional enrichment analysis, gene set enrichment analysis and comparative toxicogenomics database analysis were performed. TargetScan screened miRNAs that regulated central DEGs. A total of 305 DEGs were identified. According to gene ontology analysis, they were mainly enriched in immune system processes, extracellular regions and cytokine binding. Kyoto encyclopedia of genes and genomes analysis showed that the target cells were mainly enriched in Rap1 signal pathway, B cell receptor signal pathway and PPAR signal pathway. In the enrichment project of metascape, the reaction to bacteria, cell activation and chemotaxis can be seen in the enrichment project of gene ontology. Total 10 core genes (TYROBP, FCER1G, PLEK, LY86, IL10RA, ITGB2, LCP2, FCGR2B, CD86, CCR1) were obtained by protein-protein interaction network construction and analysis. Core genes (PLEK, LY86, IL10RA, ITGB2, and LCP2) were highly expressed in carotid AS samples and lowly expressed in normal samples. Comparative toxicogenomics database analysis showed that 5 genes were associated with pneumonia, inflammation, necrosis, and drug allergy. PLEK and LY86 genes are highly expressed in carotid AS. The higher the expression of PLEK and LY86, the worse the prognosis is.

The value of RPS15 and MRPS27 in ischemic stroke.

Ischemic stroke is caused by insufficient blood supply to the brain. It has acute onset, often disturbance of consciousness, and high mortality and disability rate. However, relationship between ribosomal proteins (RP)-S15 and mitochondrial ribosomal proteins (MRP)-S27 and ischemic stroke remains unclear. The ischemic stroke datasets GSE22255, GSE16561, and GSE199435 were downloaded from gene expression omnibus generated by GPL6883, GPL11154, and GPL570. Differentially expressed genes (DEGs) were screened, and the construction and analysis of protein-protein interaction network, functional enrichment analysis and gene set enrichment analysis were performed. The gene expression heat map was drawn. Comparative toxicogenomics database analysis were performed to find the disease most related to core gene. TargetScan screened miRNAs that regulated central DEGs. Five hundred DEGs were identified. According to gene ontology analysis, they were mainly enriched in leukocyte activation, myoid cell activation involved in immune response, cell membrane, mitochondria, secretory vesicles, catalytic activity, enzyme binding, ribonucleic acid binding, splicing. Gene set enrichment analysis showed that the enrichment items are similar to the enrichment items of differentially expressed genes. And 20 core genes were obtained. Comparative toxicogenomics database analysis showed that 6 genes (RPS15, RPS2, RPS3, MRPS27, POLR2A, MRPS26) were found to be associated with chemical and drug-induced liver injury, necrosis, delayed prenatal exposure, nephropathy, hepatomegaly and tumor. RPS15 and MRPS27 are the core genes of ischemic stroke and play an important role in ischemic stroke.

Application of Transcranial Magnetic Stimulation with Electroencephalography in the Evaluation of Brain Function Changes after Stroke.

Objective: Based on transcranial magnetic stimulation (TMS) with electroencephalography technology, this study analyzed the rehabilitation mechanism of patients' motor function reconstruction and nerve remodeling after stroke. It revealed the function of the cerebral cortex network at a deeper level and established a set of prognostic marker evaluation indicators for the reconstruction of motor function after stroke. Methods: Twenty-one patients treated at the Beijing Rehabilitation Hospital of Capital Medical University because of ischemic stroke in the territory supplied by the middle cerebral artery were selected as the experimental group. Neurophysiological evaluation, motor function evaluation, and clinical evaluation were performed 30 and 180 d after the onset of ischemic stroke. In the control group, neurophysiological evaluation was also performed as a reference index to evaluate the changes in cortical patterns after stroke. Results: The brain topographic map showed the changes in energy or power spectral density (PSD) at 1,000 ms after stimulation as compared with before stimulation, but no difference was detected in these patients. The time-frequency analysis showed that when the left primary motor cortex (M1) area was stimulated using TMS, the PSD values of the left and right M1 and posterior occipital cortex areas produced an 8-40 Hz wave band in patients S1-S11. There was no significant energy change in patients S12-S16. Conclusions: For patients with different injury types, degrees of injury, and different onset periods, individualized intervention methods should be adopted. The evaluation methods should be as diverse as possible, and the rehabilitation effects of patients should be assessed from multiple perspectives to avoid the limitations of single factors. Possible mechanism: After brain injury, the nervous system can change its structure and function through different ways and maintain it for a certain period of time. This plasticity change will change with the course of the disease.

Tailoring brain-machine interface rehabilitation training based on neural reorganization: towards personalized treatment for stroke patients.

Electroencephalogram (EEG)-based brain-machine interface (BMI) has the potential to enhance rehabilitation training efficiency, but it still remains elusive regarding how to design BMI training for heterogeneous stroke patients with varied neural reorganization. Here, we hypothesize that tailoring BMI training according to different patterns of neural reorganization can contribute to a personalized rehabilitation trajectory. Thirteen stroke patients were recruited in a 2-week personalized BMI training experiment. Clinical and behavioral measurements, as well as cortical and muscular activities, were assessed before and after training. Following treatment, significant improvements were found in motor function assessment. Three types of brain activation patterns were identified during BMI tasks, namely, bilateral widespread activation, ipsilesional focusing activation, and contralesional recruitment activation. Patients with either ipsilesional dominance or contralesional dominance can achieve recovery through personalized BMI training. Results indicate that personalized BMI training tends to connect the potentially reorganized brain areas with event-contingent proprioceptive feedback. It can also be inferred that personalization plays an important role in establishing the sensorimotor loop in BMI training. With further understanding of neural rehabilitation mechanisms, personalized treatment strategy is a promising way to improve the rehabilitation efficacy and promote the clinical use of rehabilitation robots and other neurotechnologies.

Effects of dual-task training in patients with post-stroke cognitive impairment: A randomized controlled trial.

Background: Evidence for the efficacy of cognitive-motor dual-task (CMDT) training in patients with post-stroke cognitive impairment (PSCI) and no dementia is still lacking. More importantly, although some studies on the cognitive effect of CMDT training show an improvement in cognitive performance, the results are still controversial, and the intervention mechanism of CMDT training on cognitive function improvement is not clear. The main purpose of this study was to analyze the effects of CMDT training on cognitive function, neuron electrophysiology, and frontal lobe hemodynamics in patients with PSCI. Methods: Here we tested the effects of CMDT training on cognitive function in PSCI patients. Forty subjects who met the criteria of PSCI were randomly assigned to control and experimental groups. CMDT training or cognitive task (CT) training was administered to each patient in the experimental and control groups, respectively. All subjects performed Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scale before and after the intervention, and the event-related potentials (ERP) and functional near-infrared spectroscopy (fNIRS) were used to evaluate the changes in neuron electrophysiology and hemodynamics. Results: Forty patients were randomized across Beijing Rehabilitation Hospital Capital Medical University in Beijing. At the end of the intervention, 33 subjects completed the experimental process. The CMDT group showed significant improvement in the MMSE (P = 0.01) and MoCA (P = 0.024) relative to the CT group. The results of ERP and fNIRS showed that CMDT training could shorten the latency of P300 (P = 0.001) and the peak time of oxygenated hemoglobin (P = 0.004). The results showed that CMDT training shortened the response time of central neurons and significantly increased the rate of oxygen supply to the frontal lobe. Conclusion: CMDT training in patients with PSCI improved global cognitive function, which was supported by the improved neural efficiency of associated brain areas. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2000034862.

Circ_0001360 absence alleviates oxygen-glucose deprivation/reoxygenation-induced SK-N-SH cell injury via controlling the miR-671-5p/BMF pathway.

BACKGROUND: The regulatory potency of circular RNA (circRNA) has been acknowledged in multiple human diseases, including ischaemic stroke (IS). However, only a few circRNAs were investigated in this disorder. We aimed to uncover the role of circ_0001360 in cell models of IS in vitro. METHODS: SK-N-SH cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate IS pathology conditions in vitro. Quantitative real-time PCR (qPCR) and western blot were applied for expression detection. Cell viability, proliferation and apoptosis were investigated by CCK-8, EdU and flow cytometry assays. The predicted binding of miR-671-5p to circ_0001360 or BMF 3'UTR was validated by dual-luciferase reporter and RIP assays. Proteins on the NF-κB pathway were quantified by western blot to assess NF-κB pathway activity. RESULTS: Circ_0001360 was upregulated in SK-N-SH cells after OGD/R treatment. OGD/R provoked SK-N-SH cell growth impairment, apoptosis and inflammation, while circ_0001360 knockdown relieved these injuries. Circ_0001360 targeted miR-671-5p, and miR-671-5p deficiency recovered SK-N-SH cell injury that was repressed by circ_0001360 knockdown. MiR-671-5p directly combined with BMF and repressed BMF expression. Accordingly, circ_0001360 targeted miR-671-5p to regulate the expression of BMF. Circ_0001360 knockdown weakened the phosphorylated levels of P65 and IκBα, while further miR-671-5p deficiency or BMF overexpression restored their expression levels. CONCLUSION: Circ_0001360 contributed to OGD/R-caused SK-N-SH cell injury via targeting the miR-671-5p/BMF network and activating the NF-κB pathway, thus participating in the development of IS.

Recognizing the individualized sensorimotor loop of stroke patients during BMI-supported rehabilitation training based on brain functional connectivity analysis.

BACKGROUND: Electroencephalogram (EEG) based brain-machine interaction training can facilitate rehabilitation by closing the sensorimotor loop. However, it remains unclear how to evaluate whether the loop is closed, especially for stroke patients whose brain regions of motor control and sensorimotor feedback could be altered. Our hypothesis is that motor recovery depends on whether sensorimotor loop is established poststroke. This study aims to explore how to evaluate the establishment of sensorimotor loop based on the evolving neural reorganization patterns after stroke. NEW METHOD: 14 stroke patients participated in the experiment and EEG were recorded during three specific tasks: Movement Imagery (MI), Passive Movement (PM) and Movement Execution (ME). Activated brain regions correlated with movement intention expression and sensorimotor feedback were detected respectively during MI and PM. In ME, local-averaged Phase Lag Index (PLI) was analyzed to represent the functional connectivity between activated brain regions of MI and PM. RESULTS: Individualized cortical activation was found both in MI and PM. The overlapping brain activation during PM and MI did not correlate with patient's Fugl-Meyer Upper Extremity Motor Score (FMU) . However, we found that FMU of the group with higher local-averaged PLI was statistically higher than FMU of the group with lower local-averaged PLI compared with global-averaged PLI (p < 0.05). CONCLUSIONS: The findings demonstrate functional connectivity between activated brain regions of motor control and sensorimotor feedback may imply if the individualized sensorimotor loop is established poststroke. The successful formation of the closed loop can indicate stroke patients' motor recovery.

Brain oscillatory activity correlates with the relief of post-stroke spasticity following focal vibration.

BACKGROUND: Some evidence has demonstrated that focal vibration (FV) contributes to the relief of post-stroke spasticity (PSS). Although the changes of cortical activity correlating with the relief of PSS induced by FV have been explored using transcranial magnetic stimulation, brain oscillatory activity during the above-mentioned process has not been fully understood. OBJECTIVE: The main purpose of this study is to explore the correlation between the changes in brain oscillatory activity and the relief of PSS following FV. METHODS: A clinical experiment was carried out, in which FV (87 Hz, 0.28 mm) was applied over the antagonist muscle's belly of the spastic muscle of ten chronic spastic stroke patients. An electroencephalogram was recorded following before-FV and three sessions of FV. Muscle properties to assess the relief of PSS were tested before-FV and immediately after three sessions of FV. RESULTS: EEG analysis has shown that FV can lead to the significant decrease in the relative power at C3 and C4 in the beta1 (13, 18 Hz), as well as C3 and C4 in the beta3 band (21, 30 Hz), indicating the activation of primary sensorimotor cortex (S1-M1). Muscle properties analysis has shown that, in the state of flexion of spastic muscle, muscle compliance and muscle displacement of the spastic muscle significantly increased right after FV, illustrating the relief of the spasticity. Moreover, the increase of muscle compliance is positively correlated with the reduction of difference index of the activation of bilateral S1-M1. CONCLUSIONS: This finding indicated that the relief of PSS can be associated with the activation of bilateral S1-M1 where the activation of the ipsilesional S1-M1 was higher than that of the contralesional one. This study showed the brain oscillatory activity in the bilateral S1-M1 correlating with the relief of PSS following FV, which could contribute to establishing cortex oscillatory activity as a biomarker of the relief of PSS and providing a potential mechanism explanation of the relief of PSS.

Change in knee cartilage components in stroke patients with genu recurvatum analysed by zero TE MR imaging.

Genu recurvatum in stroke patients with hemiplegia causes readily cumulative damage and degenerative changes in the knee cartilage. It is important to detect early cartilage lesions for appropriate treatment and rehabilitation. The purpose of this cross-sectional study was to provide a theoretical basis for the early rehabilitation of hemiplegia patients. We used a zero TE double-echo imaging sequence to analyse the water content in knee joint cartilage at 12 different sites of 39 stroke patients with genu recurvatum and 9 healthy volunteers using a metric similar to the porosity index. When comparing the hemiplegic limb vs. the nonhemiplegic limb in patients, the ratios of the deep/shallow free water content of the femur cartilages at the anterior horn (1.16 vs. 1.06) and posterior horn (1.13 vs. 1.25) of the lateral meniscus were significantly different. Genu recurvatum in stroke patients with hemiplegia can cause changes in the moisture content of knee cartilage, and the changes in knee cartilage are more obvious as the genu recurvatum increases. The "healthy limb" can no longer be considered truly healthy and should be considered simultaneously with the affected limb in the development of a rehabilitation treatment plan.

5 Hz rTMS improves motor-imagery based BCI classification performance.

Brain-computer interface (BCI) based rehabilitation has been proven a promising method facilitating motor recovery. Recognizing motor intention is crucial for realizing BCI rehabilitation training. Event-related desynchronization (ERD) is a kind of electroencephalogram (EEG) inherent characteristics associated with motor intention. However, due to brain deficits poststroke, some patients are not able to generate ERD, which discourages them to be involved in BCI rehabilitation training. To boost ERD during motor imagery (MI), this paper investigates the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on BCI classification performance. Eleven subjects participated in this study. The experiment consisted of two conditions: rTMS + MI versus sham rTMS + MI, which were arranged on different days. MI tests with 64-channel EEG recording were arranged immediately before and after rTMS and sham rTMS. Time-frequency analysis were utilized to measure ERD changes. Common spatial pattern was used to extract features and linear discriminant analysis was used to calculate offline classification accuracies. Paired-sample t-test and Wilcoxon signed rank tests with post-hoc analysis were used to compare performance before and after stimulation. Statistically stronger ERD (-13.93±12.99%) was found after real rTMS compared with ERD (-5.71±21.25%) before real rTMS (p<0.05). Classification accuracy after real rTMS (70.71±10.32%) tended to be higher than that before real rTMS (66.50±8.48%) (p<0.1). However, no statistical differences were found after sham stimulation. This research provides an effective method in improving BCI performance by utilizing neural modulation.Clinical Relevance- This study offers a promising treatment for patients who cannot be recruited in BCI rehabilitation training due to poor BCI classification performance.

Effects of chitosan/collagen substrates on the behavior of rat neural stem cells.

Spinal cord and brain injuries usually lead to cavity formation. The transplantation by combining stem cells and tissue engineering scaffolds has the potential to fill the cavities and replace the lost neural cells. Both chitosan and collagen have their unique characteristics. In this study, the effects of chitosan and collagen on the behavior of rat neural stem cells (at the neurosphere level) were tested in vitro in terms of cytotoxicity and supporting ability for stem cell survival, proliferation and differentiation. Under the serum-free condition, both chitosan membranes and collagen gels had low cytotoxicity to neurospheres. That is, cells migrated from neurospheres, and processes extended out from these neurospheres and the differentiated cells. Compared with the above two materials, chitosan-collagen membranes were more suitable for the co-culture with rat neural stem cells, because, except for low cytotoxicity and supporting ability for the cell survival, in this group, a large number of cells were observed to migrate out from neurospheres, and the differentiating percentage from neurospheres into neurons was significantly increased. Further modification of chitosan-collagen membranes may shed light on in vivo nerve regeneration by transplanting neural stem cells.

The effect of the dosage of NT-3/chitosan carriers on the proliferation and differentiation of neural stem cells.

This study aimed to determine the optimal dosage range of NT-3 in the soluble form or loaded with chitosan carriers by using NT-3/chitosan carriers to support the survival and proliferation of neural stem cells (NSCs) and induce them to differentiate into desired phenotypes. NSCs were co-cultured with chitosan carriers loaded with different doses of NT-3. As the control, NSCs were cultured in the defined medium, into which were added different doses of NT-3 in the soluble form every day. The ELISA kit was used to study the NT-3 releasing kinetics, which showed that, in the initial co-culture stage from 1 h to 14 weeks, the chitosan carriers loaded with different doses of NT-3 released NT-3 stably and constantly. The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was conducted to measure the cell viability, and the immunocytochemical methods were adopted to quantitatively analyze the phenotypes differentiating from the NSCs. Compared to the 100 ng NT-3 daily addition group (1400 ng over 14 days), the 25 ng, 50 ng and 200 ng NT-3 daily addition group showed dramatically shorter processes length and much lower differentiation percentage from NSCs into neurons. By contrast, the NT-3 (25 ng)-chitosan carriers group had not only higher cell viability, but also similar processes length and differentiation percentage from NSCs into neurons to the 100 ng NT-3 daily addition group. The method developed in this study significantly reduced the NT-3 amount required to support the survival, proliferation and differentiation of NSCs in vitro. Meanwhile, the chitosan carriers used here provided an ideal 3-dimensional scaffold for the adhesion, migration, proliferation and differentiation of NSC and the differentiated cells. Therefore, this method may open a new field for the large-scaled culture and amplification of NSCs in vitro to replace the lost neural cells, meanwhile lower the consumption of neurotrophic factors in the cell transplantation therapy of brain and spinal injury.

The repair of the injured adult rat hippocampus with NT-3-chitosan carriers.

The injury of the CA1 region of the adult rat hippocampus causes cognitive impairment. In this study, animal models were established by mechanically injuring the CA1 region of the adult rat hippocampus, and into the injured area were implanted chitosan carriers loaded either with or without NT-3. Immunohistochemical and nerve tracer methods were adopted to observe the role of the above-mentioned carriers in repairing the injured brain and to observe the scar formation after the injury, and Morris water maze (MWM) tests were performed to evaluate the recovery degree of the cognitive function. The results showed that NT-3-chitosan carriers stimulated regeneration of a large amount of NF-positive nerve fiber and neuron-like cells into the injured area. The newly regenerated NF-positive nerve fibers in the injured area rebuilt a neural circuit with the contralateral CA1 region via corpus callosum. Comparison of the lesion control rats and the treated rats indicates that the chitosan carriers loaded either with or without NT-3 may significantly improve the cognitive function after the hippocampus injury.