Neural Plasticity最新文献

The expression of transient receptor potential vanilloid 4 (TRPV4) channels in the brains of normal-aging individuals significantly increases. However, the involvement of TRPV4 activity in age-related memory impairment remains unknown. This study aimed to investigate the role of TRPV4 in spatial memory tasks, hippocampal inflammation, and hippocampal autophagy in adolescent, adult, and aged female rats. Rats of different ages were used: 5, 10, 19, and 19 months treated with a TRPV4 inhibitor. Memory performance was assessed using the Morris water maze (MWM). Molecular changes were evaluated through western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). The hippocampal TRPV4 expression was significantly increased in the aged rats. Furthermore, aged rats exhibited spatial memory decline, which was normalized with TRPV4 antagonist GSK2193874 (GSK219) injection. The senescence-associated β-galactosidase (SA-β-Gal) activity and hippocampal inflammatory cytokine and microglial activation marker levels in the hippocampus of aged rats were significantly increased. Similarly, the phosphoprotein marker levels of autophagy in the hippocampus of aged rats were significantly increased. GSK219 treatment effectively normalized hippocampal SA-β-Gal activity, inflammation, and autophagy in aged rats. TRPV4 hyperactivity was found to induce hippocampal inflammation and neuronal death, leading to spatial memory impairment in normal aging.

Purpose: To evaluate the efficacy and safety of platelet-rich plasma (PRP) in treating sciatic nerve injury (SNI).

Methods: A prospective, randomized, single-blind, comparative trial was conducted. Thirty patients with SNI were randomized into two groups of 15, namely, the PRP and control groups. In the PRP group, patients were injected with 5 doses of 3 mL PRP combined with 12 weeks of rehabilitation training using ultrasound guidance, while the control group received 12 weeks of rehabilitation training. Motor function recovery rating table (MFRRT) and sensory function recovery rating table (SFRRT) were used as primary outcomes. The secondary outcomes included the cross-sectional area (CSA) of the sciatic nerve under ultrasound guidance and electrophysiological assessment. Evaluations were performed at baseline and 1-, 3-, and 6-month postinjection.

Results: After treatment, there were significant differences in the motor function recovery rating, motor conduction velocity, sensory conduction velocity, and CSA of the sciatic nerve at 1, 3, and 6 months in the PRP group (p < 0.05). There were significant differences in the motor conduction velocity of the sciatic nerve at 6 months in the control group (p < 0.05).

Conclusions: PRP may be partially effective in the early repair of incomplete sciatic nerve injuries, and its efficacy could be maintained.

Background: Upper limb motor dysfunction after stroke can significantly impede activities of daily living and quality of life. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel noninvasive treatment for stroke. Its combination with rehabilitation is a growing trend.

Objective: To explore the effects of taVNS combined with rehabilitation on upper limb function poststroke.

Methods: PubMed, EMBASE, Web of Science, EBSCO, CINAHL, and the Cochrane Library databases were searched up to September 16^th, 2024. Two reviewers screened studies from these databases for eligible randomized controlled trials (RCTs) and extracted the data independently. The Cochrane collaboration tool (RoB 2.0) was used to assess the risk of bias.

Results: Four studies with 129 participants were included. Compared to controls, augmented treatment with taVNS had preferable effect on improving upper limb motor function after stroke (all outcomes: standardized mean difference [SMD] = 1.28, 95% CI: 0.65-1.90, I ² = 72%, and p  < 0.0001; Fugl-Meyer assessment [FMA]: MD = 3.66, 95% CI: 0.50-6.83, I ² = 90%, and p=0.02; Wolf Motor Function Test [WMFT]: MD = 6.77, 95% CI: -0.07 to 13.61, I ² = 88%, and p=0.05)], especially combined with conventional rehabilitation (FMA: MD = 5.91, 95% CI: 1.37-10.45, I ² = 90%, p=0.01). However, data from 3-month follow-up showed the similar therapeutic effects of rehabilitation with or without taVNS (FMA: MD = 4.66, 95% CI: -1.22 to 10.54, I ² = 93%, and p=0.12; WMFT: MD = 6.86, 95% CI: -5.91 to 19.62, I ² = 96%, and p=0.29). No obvious side effects were reported.

Conclusion: This meta-analysis showed augmented effect of taVNS on rehabilitation therapy in paretic upper limb motor function poststroke, especially combined with conventional rehabilitation. However, the high heterogeneity of aggregated results indicates more rigorously designed studies are needed.

Background and Purpose: Functional electrical stimulation (FES) is an effective therapeutic method for improving upper limb motor function after stroke, yet its usage among occupational and physical therapists in Germany remains uncertain. The aim of the study is to investigate the knowledge of, frequency of use, and barriers to electrical stimulation use in stroke rehabilitation. Methods: An online survey was conducted among German occupational and physical therapists working with stroke patients. Data were analyzed for frequency distributions, and associations between electrical stimulation usage and individual/organizational factors were assessed using Chi-Square or Fisher's exact tests. Results: A total of n = 111 participants completed the survey (57 occupational and 54 physical therapists). Almost half (45%) reported regular electrical stimulation use, with 57% wanting to increase it. Use was higher among therapists with additional training (85% vs. 44%, p=0.041), belief in electrical stimulation effectiveness during acute (87% vs. 59%, p=0.041) and early subacute stages (81% vs. 47%, p=0.027), sufficient time (78% vs. 60%, p < 0.001), and device access (80% vs. 44%, p=0.006). Therapists with over 10 years of experience used electrical stimulation less frequently (p < 0.001). Conclusion: Although electrical stimulation shows promise in rehabilitation, further research is needed to assess the resources-such as time, equipment, and therapist training-required for its effective integration.

Background: Vascular cognitive impairment (VCI) is the second most common type of cognitive impairment in the world after Alzheimer's disease (AD). At present, there is no specific drug for VCI. This study aims to confirm the role of electroacupuncture (EA) preconditioning in improving the long-term potentiation (LTP) of chronic cerebral hypoperfusion (CCH) rats with human embryonic stem cell (hESC)-derived medial ganglionic eminence (MGE) neural progenitor transplantation and to investigate its possible mechanism. Methods: Rats with two-vessel occlusion (2VO) were selected as models for the study of VCI. The rats in the 2VO + cell + EA group were given EA for 7 days after modeling. On the 7^th day, MGE neural progenitors were transplanted into the hippocampus of CCH rats. 2 weeks after transplantation, we detected the expressions of Iba1, CX3CL1/CX3CR1, Bcl2/Bax, brain-derived neurotrophic factor (BDNF), and tyrosine receptor kinase B (TrkB) in the hippocampus of rats by western blot. Immunofluorescence staining was used to observe the morphologies of microglia and the survival and differentiation of transplanted cells. Microglial morphologies were quantitatively analyzed using the AnalyzeSkeleton. 8 weeks after transplantation, the LTP in the hippocampus of brain slices was detected to evaluate the learning and memory function of the rats with CCH. Results: 2 weeks after transplantation, we observed that MGE neural progenitors survived and differentiated into neurons in the hippocampus of CCH rats. Inflammation and apoptosis appeared in the hippocampus of rats after the interruption of cerebral blood flow. EA preconditioning notably alleviated the inflammatory response and inhibited cell apoptosis in the hippocampus. Moreover, we detected that the expressions of BDNF and TrkB were increased in the hippocampus of rats in the 2VO + cell group and 2VO + cell + EA groups, especially in the 2VO + cell + EA groups. 8 weeks after transplantation, the electrophysiological experiment results showed that the LTP value in the 2VO group was 103.1% ± 2.316%. Compared with the 2VO group, LTP value increased in the 2VO + cell group and 2VO + cell + EA group, which were 136.2% ± 1.603% and 170.8% ± 15.82%, respectively. The increase of LTP value in the 2VO + cell + EA group was more obvious. Conclusion: MGE neural progenitor transplantation improves the LTP of CCH rats, and EA preconditioning can enhance the efficacy of cell transplantation. This enhancement mechanism may be attributed to the effect of EA preconditioning on ameliorating the ischemic microenvironment.

Astrocytes and metabotropic glutamate receptor 5 (mGluR5) have emerged as pivotal regulators of synaptic homeostasis and neural communication within the central nervous system (CNS). Although mGluR5 has long been considered neuron-specific, its functional expression in astrocytes is now recognized as essential for calcium (Ca²⁺) signaling, gliotransmission, and the modulation of synaptic plasticity. Dysregulation of astrocytic mGluR5 is increasingly implicated in the pathophysiology of neurodegenerative and psychiatric disorders including Alzheimer's disease (AD), Parkinson's disease (PD), depression, anxiety, and schizophrenia (SCZ) by promoting neuroinflammation, excitotoxicity, and synaptic dysfunction. In this review, we explore the emerging role of astrocytic mGluR5 in mediating astrocyte-neuron communication and its maladaptive regulation in disease contexts. We also assess the therapeutic potential of targeting astrocytic mGluR5, highlighting advances in pharmacological modulators, gene therapy, and RNA-based strategies aimed at restoring homeostatic function. Despite recent progress, critical knowledge gaps remain, particularly regarding the regional specificity of astrocytic mGluR5 effects, its crosstalk with other signaling pathways, and its contribution to chronic neuroinflammation. Addressing these challenges may unlock innovative astrocyte-targeted therapies to restore synaptic integrity and protect against neurodegeneration in CNS disorders.

Astrocytes play a crucial role in ensuring neuronal survival and function. In stroke, astrocytes trigger the unfolded protein response (UPR) to restore endoplasmic reticulum homeostasis. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified endoplasmic reticulum stress-induced neurotrophic factor, attenuates cerebral ischemic injury by reducing inflammatory responses. The mechanisms by which astrocytes regulate MANF expression and the role of MANF in modulating inflammation remain to be elucidated. In this study, we constructed middle cerebral artery occlusion (MCAO)/reperfusion model in C57BL/6J mice and an oxygen glucose deprivation/reoxygenation model in a neuronal and astrocyte coculture system. The present study utilized an intraventricular injection of adeno-associated virus (AAV) to effectively block the PERK pathway in astrocytes. Moreover, MANF-siRNA was employed to suppress endogenous MANF expression, while rhMANF was used as an exogenous supplement. 2,3,5-Triphenyltetrazolium chloride (TTC), modified neurological severity score (mNSS), adhesive removal test, Golgi staining, hematoxylin-eosin (HE) staining, western blot, and enzyme-linked immunosorbent assay (ELISA) were applied to evaluate the protective effects of PERK pathway and the expression of MANF in astrocytes. In vitro experiments, ELISA, cell counting kit-8 (CCK-8), and western blot were used to detect the mechanisms by which MANF regulates neuroinflammation. The results showed that blocking the astrocytic PERK pathway decreased MANF expression, aggravated synaptic loss, and exacerbated infarct volume and neurological outcomes. Conversely, cellular experiments showed that activation of PERK increased MANF expression, promoted synaptic protein expression, and increased neuronal cell viability. Additionally, increasing exogenous MANF inhibited STAT3 phosphorylation, reduced the release of inflammatory factors, and improved neuronal cell viability. In conclusion, our study demonstrates that after stroke, astrocytes activate PERK and upregulate MANF expression, which inhibits STAT3 phosphorylation, reduces proinflammatory cytokine release, rescues neuronal synapse loss, and promotes the recovery of neurological function in mice.

Purpose: Strength gains and synergistic muscle group activations due to expiratory muscle strength training (EMST) lead to beneficial changes in several upper aerodigestive functions, including swallowing; however, there may be a potential top-down influence through neuroplasticity. The current study investigated changes in brain activation patterns during swallowing tasks before and after 4 weeks of EMST. Methods: Five right-handed, healthy young adult men aged 19-35 (mean = 28.8, SD = 2.68) participated in 4 weeks of EMST. All participants performed a swallow task, and blood-oxygen level-dependent (BOLD) responses were obtained at baseline and post-training conditions using functional magnetic resonance imaging (fMRI). Results: We observed a significant increase in activation across 12 regions, including the left primary somatosensory cortex (S1), left primary motor cortex (M1), bilateral supplementary motor areas (SMAs), bilateral cerebellum, right middle frontal gyrus, insula, anterior cingulate, and thalamus, following 4 weeks of EMST. While activations in several regions implicated with swallowing were expected, we also observed strong activation in areas associated with motor learning and cognitive functions. Conclusion: Our study's results provide preliminary evidence that EMST can modulate neural networks associated with swallowing. We speculate that enhanced sensorimotor excitability and cortical representation, motor learning, and improved cognitive-sensorimotor integration contribute to EMST's multidomain benefits. Furthermore, our findings suggest that EMST may offer potential cognitive and neuroprotective benefits beyond improving upper aerodigestive functions.

Transcranial direct current stimulation (tDCS) and transcutaneous electrical nerve stimulation (TENS) are both recognized for their analgesic effects; however, evidence suggests limitations in their efficacy when applied to knee osteoarthritis (KOA) after stroke. This study aimed to assess the efficacy and cortical activity impact of a dual-target electrical stimulation approach combining tDCS and TENS in the treatment of KOA after stroke. We hypothesized that the combination of tDCS with TENS could more effectively address KOA after stroke by enhancing brain activity through the induction of neural oscillations. To test this hypothesis, a double-blind, randomized trial was conducted with 30 participants receiving either TENS + tDCS or TENS + sham tDCS over an 8-week period, from Monday to Friday. Electroencephalograms (EEGs), Brief Pain Inventory (BPI), visual analog scale (VAS), stride length, cadence, 6-min walk test (6 MWT), knee range of motion (ROM), and quadriceps strength were collected pre- and poststimulation. Pain indicators were analyzed using t-tests for continuous variables and chi-square tests for categorical variables, with repeated measures ANOVA employed to explore changes and interactions over time. For EEG analysis, paired t-tests were utilized to investigate changes in brain regions before and after treatment on the affected side, with visual analysis conducted subsequently. The results indicated that the combined treatment led to significant improvements in the affected hemisphere, with significant changes observed in α1, α2, and β power. Additionally, significant group× time interaction effects were noted for BPI, VAS, stride length, cadence, and 6MWT. The study concludes that dual-target electrostimulation using tDCS combined with TENS significantly ameliorates knee joint inflammation following stroke by acting on the cerebral cortex and target organs. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2200064735.

Background: Rehabilitation methods that include anodal transcranial direct current stimulation (atDCS) and extended reality (XR) exercises have been used to enhance neural networks and improve functional performance in stroke patients, but the neuromuscular and neurophysiological mechanisms underlying these improvements are not fully understood. The purpose of this study was to examine the effects of atDCS during XR rehabilitation exercises on cortical, neuromuscular, and clinical outcomes of stroke survivors. Methods: Nineteen chronic stroke survivors were placed into either a transcranial direct current stimulation (tDCS) or a Sham group, without significant (p > 0.73) differences in the baseline levels of disability between groups. The tDCS group received active atDCS and the Sham group received sham atDCS applied on the ipsilesional primary motor cortex (M1) while performing a 10-session XR rehabilitation program. Surface electromyography (EMG) activity was recorded from deltoid and rectus femoris of the paretic limb without and with the application of active/sham atDCS on the M1. Shoulder abduction and hip flexion active maximum joint range of motion (ROM_max), electroencephalography (EEG)-derived brain symmetry index (BSI) and functional/clinical tests were assessed before and after the rehabilitation program. Results: EMG activity was ~ 31% greater during hip flexion of the paretic limb with the application of active atDCS than without atDCS (p=0.04). Paretic hip flexion ROM_max increased by ~ 26%, BSI decreased by ~ 72% (indicating greater brain symmetry) and timed up and go (TUG) functional test improved by ~ 11% from before to after the rehabilitation program for the tDCS group only (p < 0.05). No other significant differences (p > 0.05) were observed. Conclusion: It seems that the application of active atDCS targeted the ipsilesional M1 representation of the quadriceps, which potentiated muscle activation in the paretic rectus femoris during XR exercises and resulted in greater motor recovery in hip flexion movements. The EEG-derived BSI results also indicate that atDCS was effective in reorganizing the ipsilesional hemisphere brain activity after stroke.