Neural Plasticity最新文献

[This retracts the article DOI: 10.1155/2021/4516133.].

Stroke is a major health problem worldwide, with numerous health, social, and economic implications for survivors and their families. One simple answer to this problem would be to ensure the best rehabilitation with full social reintegration. As such, a plethora of rehabilitation programs was developed and used by healthcare professionals. Among them, modern techniques such as transcranial magnetic stimulation and transcranial direct current stimulation are being used and seem to bring improvements to poststroke rehabilitation. This success is attributed to their capacity to enhance cellular neuromodulation. This modulation includes the reduction of the inflammatory response, autophagy suppression, antiapoptotic effects, angiogenesis enhancement, alterations in the blood-brain barrier permeability, attenuation of oxidative stress, influence on neurotransmitter metabolism, neurogenesis, and enhanced structural neuroplasticity. The favorable effects have been demonstrated at the cellular level in animal models and are supported by clinical studies. Thus, these methods proved to reduce infarct volumes and to improve motor performance, deglutition, functional independence, and high-order cerebral functions (i.e., aphasia and heminegligence). However, as with every therapeutic method, these techniques can also have limitations. Their regimen of administration, the phase of the stroke at which they are applied, and the patients' characteristics (i.e., genotype and corticospinal integrity) seem to influence the outcome. Thus, no response or even worsening effects were obtained under certain circumstances both in animal stroke model studies and in clinical trials. Overall, weighing up risks and benefits, the new transcranial electrical and magnetic stimulation techniques can represent effective tools with which to improve the patients' recovery after stroke, with minimal to no adverse effects. Here, we discuss their effects and the molecular and cellular events underlying their effects as well as their clinical implications.

Depression is a highly prevalent and heterogeneous disorder that requires new strategies to overcome depression. In this study, we aimed to investigate whether leonurine modulated hippocampal nerve regeneration in chronic and unpredictable mild stress (CUMS) rats through the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis. The CUMS rat model was constructed and treated with leonurine. The body weight of rats was recorded, and a series of tests were performed. Western blot was utilized to measure the expression of BDNF and 5-HT in the hippocampus. Then the expression of SHH, GLI, PTCH, and SMO were measured by qRT-PCR and western blot. The colocalization of BrdU+DCX and BrdU+NeuN was evaluated by IF. 16S rDNA high-throughput sequencing was applied to detect the composition and distribution of gut microbiota. The differential metabolites were analyzed by untargeted metabolomics. The correlation between gut microbiota and microbial metabolites was analyzed by Pearson correlation coefficient. After CUMS modeling, the body weight of rats was decreased, and the expression of BDNF and 5-HT were decreased, while the body weight was recovered, and the expression of BDNF and 5-HT were increased after leonurine treatment. Leonurine reversed the reduction in the colocalization of BrdU+DCX and BrdU+NeuN and the reduction in the levels of SHH, GLI, PTCH, and SMO induced by CUMS modeling. Leonurine also restored gut microbiota and microbial metabolites homeostasis in CUMS rats. Furthermore, Prevotellaceae_Ga6A1_group was negatively correlated with 3-Oxocholic acid, nutriacholic acid, and cholic acid. Collectively, leonurine regulated hippocampal nerve regeneration in CUMS rats by activating the SHH/GLI signaling pathway and restoring gut microbiota and microbial metabolic homeostasis.

Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1β, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.

Introduction: The risk of falling and its subsequent injuries increases with aging. Impaired balance and gait are important contributing factors to the increased risk of falling. A wide range of methods was examined to improve balance, but these interventions might produce small effects or be inapplicable for this population. The current study aimed at investigating the effect of motor imaginary (MI) training combined with transcranial direct current stimulation (tDCS) over the cerebellum on balance in middle-aged women with high fall risk.

Methods: Thirty subjects aged 40-65 years old were divided into two groups including intervention (n = 15) and sham control (n = 15). The participants completed a 4-week program 3 times per week. The intervention group performed MI training combined with tDCS over the cerebellum, and the control group performed MI training combined with sham tDCS over the cerebellum. Static and dynamic balance were measured at baseline and after completing the 4-week program using balance error scoring system (BESS) and Y balance testing, respectively.

Result: A one-way analysis of covariance and paired t-tests were used to analyze the data. Significant improvement was observed in both balance tests in the intervention group after the implementation of the 4-week intervention program compared to the control group. The within-group analysis showed that both static and dynamic balance improved significantly from the baseline values only in the intervention group (p < 0.05) and not in the control group (p > 0.05).

Conclusion: The results of the study indicate that MI training combined with tDCS over the cerebellum can lead to balance improvement in middle-aged women with high fall risk.

High-fat diet- (HFD-) induced neuroinflammation may ultimately lead to an increased risk of cognitive impairment. Here, we evaluate the effects of diet control and swimming or both on the prevention of cognitive impairment by enhancing SIRT1 activity. Twenty-week-old ApoE-/- mice were fed a HFD for 8 weeks and then were treated with diet control and/or swimming for 8 weeks. Cognitive function was assessed using the novel object recognition test (NORT) and Y-maze test. The expression of sirtuin-1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), brain-derived neurotrophic factor (BDNF), nuclear factor kappa B p65 (NF-κB p65), interleukin-1β (IL-1β), and tumour necrosis factor-α (TNF-α) in the hippocampus was measured by western blotting. The levels of fractional anisotropy (FA), N-acetylaspartate (NAA)/creatine (Cr) ratio, choline (Cho)/Cr ratio, and myo-inositol (MI)/Cr ratio in the hippocampus were evaluated by diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) using 7.0-T magnetic resonance imaging (MRI). Our results showed that cognitive dysfunction and hippocampal neuroinflammation appeared to be remarkably observed in apolipoprotein E (ApoE)-/- mice fed with HFD. Diet control plus swimming significantly reversed HFD-induced cognitive decline, reduced the time spent exploring the novel object, and ameliorated spontaneous alternation in the Y-maze test. Compared with the HFD group, ApoE-/- mice fed diet control and/or subjected to swimming had an increase in FA, NAA/Cr, and Cho/Cr; a drop in MI/Cr; elevated expression levels of SIRT1, PGC-1α, and BDNF; and inhibited production of proinflammatory cytokines, including NF-κB p65, IL-1β, and TNF-α. SIRT1, an NAD⁺-dependent class III histone enzyme, deacetylases and regulates the activity of PGC-1α and NF-κB. These data indicated that diet control and/or swimming ameliorate cognitive deficits through the inhibitory effect of neuroinflammation via SIRT1-mediated pathways, strongly suggesting that swimming and/or diet control could be potentially effective nonpharmacological treatments for cognitive impairment.

Hypoxic-ischemic white matter injury (WMI) pathogenesis in preterm infants is not well established, and iron-related proteins in the brain may play an important role in imbalanced iron metabolism. We aimed to investigate the iron-related protein changes in neonatal rats after hypoxia-ischemia (HI), clarify the role of iron-related proteins in hypoxic-ischemic WMI, and potentially provide a new target for the clinical treatment of hypoxic-ischemic WMI in preterm infants. We adopted a WMI animal model of bilateral common carotid artery electrocoagulation combined with hypoxia in neonatal 3-day-old Sprague-Dawley rats. We observed basic myelin protein (MBP) and iron-related protein expression in the brain (ferritin, transferrin receptor [TfR], and membrane iron transporter 1 [FPN1]) via Western blot and double immunofluorescence staining. The expression of MBP in the WMI group was significantly downregulated on postoperative days (PODs) 14, 28, and 56. Ferritin levels were significantly increased on PODs 3, 7, 14, and 28 and were most significant on POD 28, returning to the sham group level on POD 56. FPN1 levels were significantly increased on PODs 7, 28, and 56 and were still higher than those in the sham group on POD 56. TfR expression was significantly upregulated on PODs 1, 7, and 28 and returned to the sham group level on POD 56. Immunofluorescence staining showed that ferritin, TfR, and FPN1 were expressed in neurons, blood vessels, and oligodendrocytes in the cortex and corpus callosum on POD 28. Compared with the sham group, the immune-positive markers of three proteins in the WMI group were significantly increased. The expression of iron-related proteins in the brain (ferritin, FPN1, and TfR) showed spatiotemporal dynamic changes and may play an important role in hypoxic-ischemic WMI.

During growth and aging, the role of the hippocampus in memory depends on its interactions with related brain regions. Particularly, two subregions, anterior hippocampus (aHipp) and posterior hippocampus (pHipp), play different and critical roles in memory processing. However, age-related changes of hippocampus subregions on structure and function are still unclear. Here, we investigated age-related structural and functional characteristics of 106 participants (7-85 years old) in resting state based on fractional anisotropy (FA) and functional connectivity (FC) in aHipp and pHipp in the lifespan. The correlation between FA and FC was also explored to identify the coupling. Furthermore, the Wechsler Abbreviated Scale of Intelligence (WASI) was used to explore the relationship between cognitive ability and hippocampal changes. Results showed that there was functional separation and integration in aHipp and pHipp, and the number of functional connections in pHipp was more than that in aHipp across the lifespan. The age-related FC changes showed four different trends (U-shaped/inverted U-shaped/linear upward/linear downward). And around the age of 40 was a critical period for transformation. Then, FA analyses indicated that all effects of age on the hippocampal structures were nonlinear, and the white matter integrity of pHipp was higher than that of aHipp. In the functional-structural coupling, we found that the age-related FA of the right aHipp (aHipp.R) was negatively related to the FC. Finally, through the WASI, we found that the age-related FA of the left aHipp (aHipp.L) was positively correlated with verbal IQ (VERB) and vocabulary comprehension (VOCAB.T), the FA of aHipp.R was only positively correlated with VERB, and the FA of the left pHipp (pHipp.L) was only positively correlated with VOCAB.T. These FC and FA results supported that age-related normal memory changes were closely related to the hippocampus subregions. We also provided empirical evidence that memory ability was altered with the hippocampus, and its efficiency tended to decline after age 40.

Methods: A pilot double-blind and randomized clinical trial. Ninety-one subjects with subacute stroke were treated with cathodal/sham stimulation tDCS based on CGR (physiotherapy 40 min/d and occupational therapy 20 min/d) once daily for 20 consecutive working days. Computer-based stratified randomization (1 : 1) was employed by considering age and sex, with concealed assignments in opaque envelopes to ensure no allocation errors after disclosure at the study's end. Patients were evaluated at T0 before treatment, T1 immediately after the posttreatment assessment, and T2 assessment one month after the end of the treatment. The primary outcome index was assessed: lower limb Fugl-Meyer motor score (FMA-LE); secondary endpoints were other gait assessment and relevant stroke scale assessment.

Results: Patients in the trial group performed significantly better than the control group in all primary outcome indicators assessed posttreatment T1 and at follow-up T2: FMA-LE outcome indicators between the two groups in T1 (P = 0.032; effect size 1.00, 95% CI: 0.00 to 2.00) and FMA-LE outcome indicators between the two groups in T2 (P = 0.010; effect size 2.00, 95% CI: 1.00 to 3.00).

Conclusion: In the current pilot study, ctDCS plus CGR was an effective treatment modality to improve lower limb motor function with subacute stroke. The effectiveness of cathodal tDCS in poststroke lower limb motor dysfunction is inconclusive. Therefore, a large randomized controlled trial is needed to verify its effectiveness.