Neural Plasticity最新文献

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.

Spinal cord injury (SCI) is a severe condition that affects the central nervous system (CNS), for which there is currently no effective treatment. Schwann cells (SCs) transplantation for SCI has been well demonstrated in preclinical studies, showing that it can achieve therapeutic goals by improving autonomic function, reducing neuropathic pain, and enhancing limb function through mechanisms such as alleviating inflammation, modulating immunity, and reducing dense scar formation. However, the transplantation of SCs sometimes encounters adverse events, such as low survival rates, significant rejection reactions, limitations on transplantation methods, and the formation of glial scars, all of which severely hinder its clinical application. Meanwhile, SC-derived exosomes (SC-exos) also hold great potential in treating SCI, with specific roles, including immune modulation, anti-inflammatory effects, angiogenesis, apoptosis inhibition, and promotion of axonal regeneration, even surpassing traditional cell therapy in certain aspects. This paper aims to elucidate the potential mechanisms and valuable therapeutic roles of SCs and SC-exos in the treatment of SCI, as well as to provide insights for subsequent research directions by analyzing their current limitations.

Background and Purpose: Intermittent theta-burst stimulation (iTBS) targeting the cerebellum represents a promising therapeutic approach, demonstrating efficacy in the rehabilitation of motor and cognitive impairments after stroke. This study aims to evaluate the real-time and immediate effects of cerebellar iTBS on the cerebral cortex of stroke patients. Methods: This study was conducted in a crossover design, initiating with sham-iTBS followed by iTBS after a 24-h washout period. The functional near-infrared spectroscopy (fNIRS) was applied to observe cortical activation from cerebellar iTBS in stroke patients and changes in resting-state functional connectivity (FC) and amplitude of low-frequency fluctuations (ALFF) poststimulation. Results: Compared to sham stimulation, significant enhancement of cortical activation was observed in the left dorsolateral prefrontal cortex (DLPFC; Channel 26, t = 2.47, p=0.036, Cohen's d = 0.783) and left primary motor cortex (PMC; Channel 61, t = 2.88, p=0.018, Cohen's d = 0.907; Channel 62, t = 2.62, p=0.028, Cohen's d = 0.826). Compared to the resting period after sham-iTBS, the resting period following iTBS demonstrated significantly enhanced FC between the temporal cortex (TC) and the somatosensory cortex (SSC) (p=0.029), as well as between the frontal eye field (FEF) and the PMC (p=0.031). Additionally, the ALFF value of the medial superior frontal gyrus (SFGmed) also increased significantly during the resting period after iTBS (Channel 20, t = 5.79, p=0.027, Cohen's d = 0.63). Conclusion: The application of iTBS to the cerebellum significantly enhances the activation of cognitive and motor areas in the cerebral cortex. Additionally, improved FC between brain regions and increased spontaneous neuronal activity were observed following stimulation. These findings reveal the potential mechanisms by which cerebellar iTBS may facilitate functional recovery in stroke patients.

Purpose: This study aims to investigate functional abnormalities in transient ischemic attack (TIA) patients compared to healthy controls (HCs) using percent amplitude of fluctuation (PerAF) across multiple frequency bands derived from resting-state functional magnetic resonance imaging (rs-fMRI). Methods: We scanned 48 TIA patients and 41 HCs using rs-fMRI and high-resolution T1-weighted brain images. Both PerAF and modified PerAF (mPerAF) were utilized for comparative analysis across the typical frequency band (0.01-0.08 Hz) and two subfrequency bands: slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz). Two-sample t-tests were conducted to assess group differences, with multiple comparisons correction using Gaussian random field (GRF) methods. Results: Compared to HCs, TIA patients exhibited significantly lower PerAF in the right inferior frontal triangular gyrus in both the typical and slow-5 bands. Additionally, reductions were observed in the right superior frontal medial gyrus in the slow-4 band and the left middle temporal gyrus in the slow-5 band. No significant differences were observed in mPerAF. Conclusion: These findings suggest a significant impact of TIA on multiple brain regions, with frequency-specific alterations in PerAF, providing novel insights into the underlying mechanisms of TIA.

This study examined blood oxygenation changes during a modified Stroop task with colored Chinese words using functional near-infrared spectroscopy (fNIRS) in patients with poststroke aphasia. The task included three conditions: neutral, congruent, and incongruent. Participants consisted of 15 healthy adults and 15 patients with poststroke aphasia. Compared to healthy adults, aphasic patients showed significantly longer reaction times and reduced accuracy across all conditions, with a more pronounced interference effect in the incongruent condition. fNIRS analysis revealed distinct neurophysiological differences: decreased activation in Broca's area, increased activation in the ventromedial frontal pole, and atypical recruitment of the left dorsolateral prefrontal cortex (DLPFC) during Stroop interference tasks. These findings highlight the differing neural mechanisms underlying cognitive interference in poststroke aphasia. The integration of fNIRS with the Stroop task enhances our understanding of intentional inhibition deficits and the impact of cognitive interference in aphasic patients. Importantly, these results suggest that deficits in cognitive control and abnormalities in prefrontal regions, such as the frontal pole and DLPFC, may be potential targets for noninvasive neuromodulation to improve cognitive control in poststroke aphasia. The observed atypical activation patterns in these regions underscore their critical role in managing cognitive interference and intentional inhibition. Noninvasive brain modulation techniques may offer promising strategies for modulating these neural mechanisms. This study underscores the need for targeted interventions that address prefrontal dysfunctions and emphasizes the value of visual language tasks in exploring the complex relationship between language deficits and cognitive control in this population.