Neural Plasticity最新文献

Peripheral nerve injury leads to severe neuropathic pain. Previous studies have highlighted the beneficial effects of physical exercise on alleviating neuropathic pain. Exercise regulating transforming growth factor-β1 (TGF-β1) can improve several diseases and relieve neuropathic pain induced by peripheral nerve injury. Here, we investigated whether exercise could alleviate neuropathic pain by modulating TGF-β1 expression. We assessed mechanical and cold pain behavior and conducted molecular evaluation of the spinal cord. We found that spared nerve injury (SNI) led to mechanical and cold allodynia in the hind paw, elevated the expression of latency-associated peptide- (LAP-) TGF-β1, and activated astroglial in the spinal cord. Exercise decreases allodynia, astroglial activation, and LAP-TGF-β1 in SNI mice. Intrathecal injection of a TGF-type I receptor inhibitor attenuated exercise analgesia and enhanced astroglial activation. These findings demonstrate that exercise induces analgesia by promoting TGF-β1 activation and inhibiting astrogliosis. Our study reveals a new underlying mechanism for exercise-attenuated neuropathic pain in the maintenance stage of neuropathic pain after nerve injury.

Ototoxic hearing loss results from hair cell death via reactive oxygen species (ROS) overproduction and consequent apoptosis. We investigated the effects of vitamin C (VC) on neomycin-induced HEI-OC1 cell damage, as well as the mechanism of inhibition. HEI-OC1 cells were treated with neomycin or with vitamin C (VC). The results indicated that VC had a protective effect on neomycin-induced HEI-OC1 cell death. Mechanistically, VC decreased neomycin-induced ROS generation, suppressed cell death, and increased cell viability. VC inhibited neomycin-induced apoptosis, ameliorated neomycin reduced antiapoptotic Bcl-2 expression, and suppressed neomycin increased expression of proapoptotic Bax, caspase-3 cleavage and caspase-8. TUNEL labeling demonstrated that VC blocked neomycin-induced apoptosis. Further study revealed that the effect of VC on neomycin-induced hair cell death was through interference with JNK activation and p38 phosphorylation. These results indicate that VC via suppressed ROS generation, which inhibited cell death by counteracting apoptotic signaling induced by neomycin in cells. Hence, VC is a potential candidate for protection agent against neomycin-induced HEI-OC1 cell ototoxicity.

Neurodegenerative diseases, such as Alzheimer's disease (AD), and their associated deterioration of cognitive function are common causes of disability. The slowly developing pathology of neurodegenerative diseases necessitates early diagnosis and monitored long-term treatment. Lack of effective therapies coupled with an improved rate of early diagnosis in our aging population have created an urgent need for the development of novel drugs, as well as the need for reliable biomarkers for treatment response. These issues are especially relevant for AD, in which the rate of clinical trial drug failures has been very high. Frequently used biomarker evaluation procedures, such as positron emission tomography or cerebrospinal fluid measurements of phospho-tau and amyloid beta, are invasive and costly, and not universally available or accessible. This review considers the functionality of the event-related potential (ERP) P300 methodology as a surrogate biomarker for predicting the procognitive potential of drugs in clinical development for neurocognitive disorders. Through the application of standardized electroencephalography (EEG) described here, ERP P300 can be reliably measured. The P300 waveform objectively measures large-scale neuronal network functioning and working memory processes. Increased ERP P300 latency has been reported throughout the literature in disorders of cognition, supporting the potential utility of ERP P300 as a biomarker in many neurological and neuropsychiatric disorders, including AD. Specifically, evidence presented here supports ERP P300 latency as a quantitative, unbiased measure for detecting changes in cognition in patients with AD dementia through the progression from mild to moderate cognitive impairment and after drug treatment.

Objective: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DOC). However, its therapeutic effects in the literature are inconsistently documented. The primary aim of this study was to explore the alterations in neural connectivity and neurobehavioral reactivity during rTMS modulation in patients with DOC. In addition, safety was investigated as a secondary aim.

Methods: The presence of bilateral N20 components in DOC patients was determined by somatosensory-evoked potential (SEP) before enrollment in the study. A total of 64 patients were enrolled and randomly placed into the active and sham groups. Ultimately, 50 patients completed the study. Twenty-five patients in the active group underwent real HF-rTMS, and 25 patients in the sham group underwent sham HF-rTMS, which was delivered over the left dorsolateral prefrontal cortex (DLPFC). The outcome measures of performed pre- and postintervention included the latencies of the N20 and N20-P25 amplitudes of SEP, brainstem auditory-evoked potential (BAEP) grade, JFK Coma Recovery Scale-Revised (CRS-R) score, and Glasgow Coma Scale (GCS) score; any adverse events were recorded at any time during the intervention.

Result: Following six weeks of treatment, a significant increase was observed in the total CRS-R and GCS scores, and the N20-P25 amplitudes of patients in the two groups were compared with that obtained from preintervention (all p values < 0.05). The waves of BAEP in the two groups also showed a trend toward normalized activity compared with preintervention grades (p values < 0.05). A significant decrease in the latencies of N20 (p values < 0.001) was observed in the active group compared with measurements obtained from preintervention, whereas no significant decrease was observed in the sham group (p values = 0.013). The improvement in total CRS-R scores (p values = 0.002), total GCS scores (p values = 0.023), and N20-P25 amplitudes (p values = 0.011) as well as the decrease in latencies of N20 (p values = 0.018) and change in BAEP grades (p values = 0.013) were significantly different between the two groups. The parameters in neural connectivity (N20-P25 amplitudes, N20 latencies, and BAEP grades) were significantly correlated with the total CRS-R and GCS scores at postintervention, and the changes of CRS-R before and after interventions have a positive relationship with N20-P25 amplitudes. No adverse events related to the rTMS protocol were recorded.

Conclusion: Neural connectivity levels are affected by HF-rTMS and are significantly related to clinical responses in DOC patients with the presence of bilateral N20. The elevation of neural connectivity levels may lay a foundation for successful HF-rTMS treatment for DO

Background: Rehabilitation of upper extremity hemiplegia after stroke remains a great clinical challenge, with only 20% of patients achieving a basic return to normal hand function. How to promote the recovery of motor function at an early stage is crucial to the life of the patient.

Objectives: To invest the effects of additional mirror therapy in improving upper limb motor function and activities of daily living in acute and subacute stroke patients, and further explore the effects of other factors on the efficacy of MT.

Methods: Participants who presented with unilateral upper extremity paralysis due to a first ischemic or hemorrhagic stroke were included in the study. They were randomly allocated to the experimental or control group. Patients in the control group received occupational therapy for 30 minutes each session, six times a week, for three weeks, while patients in the experimental group received 30 minutes of additional mirror therapy based on occupational therapy. The primary outcome measures were Fugl-Meyer Assessment-upper extremity (FMA-UE), Action Research Arm Test (ARAT), and Instrumental Activity of Daily Living (IADL) which were evaluated by two independent occupational therapists before treatment and after 3-week treatment. A paired t-test was used to compare the values between pretreatment and posttreatment within an individual group. Two-sample t-test was utilized to compare the changes (baseline to postintervention) between the two groups.

Results: A total of 52 stroke patients with unilateral upper extremity motor dysfunction who were able to actively cooperate with the training were included in this study. At baseline, no significant differences were found between groups regarding demographic and clinical characteristics (P > 0.05 for all). Upper limb motor function and ability to perform activities of daily living of the patients were statistically improved in both groups towards the third week (P < 0.05). In addition, statistical analyses showed more significant improvements in the score changes of FMA-UE and IADL in the experimental group compared to the control group after treatment (P < 0.05), but no significant difference was observed in the ARAT score changes between the two groups (P > 0.05). The subgroup analysis showed that no significant heterogeneity was observed in age, stroke type, lesion side, and clinical stage (P > 0.05).

Conclusion: In conclusion, some positive changes in aspects of upper limb motor function and the ability to perform instrumental activities of daily living compared with routine occupational therapy were observed in additional mirror therapy. Therefore, the application of additional mirror therapy training should be reconsidered to improve upper extremity motor in stroke patients.

Previous functional magnetic resonance imaging (fMRI) analyses have shown that the dorsal attention network (DAN) is involved in the pathophysiological changes of tinnitus, but few relevant studies have been conducted, and the conclusions to date are not uniform. The purpose of this research was to test whether there is a change in intrinsic functional connectivity (FC) patterns between the DAN and other brain regions in tinnitus patients. Thirty-one patients with persistent tinnitus and thirty-three healthy controls were enrolled in this study. A group independent component analysis (ICA), degree centrality (DC) analysis, and seed-based FC analysis were conducted. In the group ICA, the tinnitus patients showed increased connectivity in the left superior parietal gyrus in the DAN compared to the healthy controls. Compared with the healthy controls, the tinnitus patients showed increased DC in the left inferior parietal gyrus and decreased DC in the left precuneus within the DAN. The clusters within the DAN with significant differences in the ICA or DC analysis between the tinnitus patients and the healthy controls were selected as regions of interest (ROIs) for seeds. The tinnitus patients exhibited significantly increased FC from the left superior parietal gyrus to several brain regions, including the left inferior parietal gyrus, the left superior marginal gyrus, and the right superior frontal gyrus, and decreased FC to the right anterior cingulate cortex. The tinnitus patients exhibited decreased FC from the left precuneus to the left inferior occipital gyrus, left calcarine cortex, and left superior frontal gyrus compared with the healthy controls. The findings of this study show that compared with healthy controls, tinnitus patients have altered functional connections not only within the DAN but also between the DAN and other brain regions. These results suggest that it may be possible to improve the disturbance and influence of tinnitus by regulating the DAN.

Purpose: To compare the effectiveness of contralaterally controlled functional electrical stimulation (CCFES) versus neuromuscular electrical stimulation (NMES) on motor recovery of the upper limb in subacute stroke patients.

Materials and methods: Fifty patients within six months poststroke were randomly assigned to the CCFES group (n = 25) and the NMES group (n = 25). Both groups underwent routine rehabilitation plus 20-minute stimulation on wrist extensors per day, five days a week, for 3 weeks. Fugl-Meyer Assessment of upper extremity (FMA-UE), action research arm test (ARAT), Barthel Index (BI), and surface electromyography (sEMG) were assessed at baseline and end of intervention.

Results: After a 3-week intervention, FMA-UE and BI increased in both groups (p < 0.05). ARAT increased significantly only in the CCFES group (p < 0.05). The changes of FMA-UE, ARAT, and BI in the CCFES group were not greater than those in the NMES group. The improvement in sEMG response of extensor carpi radialis by CCFES was greater than that by NMES (p = 0.026). The cocontraction ratio (CCR) of flexor carpi radialis did not decrease in both groups.

Conclusions: CCFES improved upper limb motor function, but did not show better treatment effect than NMES. CCFES significantly enhanced the sEMG response of paretic extensor carpi radialis compared with NMES, but did not decrease the cocontraction of antagonist.

As the final level of the binaural integration center in the subcortical nucleus, the inferior colliculus (IC) plays an essential role in receiving binaural information input. Previous studies have focused on how interactions between the bilateral IC affect the firing rate of IC neurons. However, little is known concerning how the interactions within the bilateral IC affect neuron latency. In this study, we explored the synaptic mechanism of the effect of bilateral IC interactions on the latency of IC neurons. We used whole-cell patch clamp recordings to assess synaptic responses in isolated brain slices of Kunming mice. The results demonstrated that the excitation-inhibition projection was the main projection between the bilateral IC. Also, the bilateral IC interactions could change the reaction latency of most neurons to different degrees. The variation in latency was related to the type of synaptic input and the relative intensity of the excitation and inhibition. Furthermore, the latency variation also was caused by the duration change of the first subthreshold depolarization firing response of the neurons. The distribution characteristics of the different types of synaptic input also differed. Excitatory-inhibitory neurons were widely distributed in the IC dorsal and central nuclei, while excitatory neurons were relatively concentrated in these two nuclei. Inhibitory neurons did not exhibit any apparent distribution trend due to the small number of assessed neurons. These results provided an experimental reference to reveal the modulatory functions of bilateral IC projections.

Objectives: Functional prognosis is potentially correlated with gut microbiota alterations following the dysregulation of the gut-microbiota-brain axis after stroke. This study was designed to explore the poststroke alterations of gut microbiota and potential correlations between gut microbiota and global functions.

Methods: A total of thirty-eight patients with stroke and thirty-five healthy demographics-matched controls were recruited. Their fecal DNAs were extracted, and the V3-V4 regions of the conserved bacterial 16S RNA were amplified and sequenced on the Illumina MiSeq platform. Microbial composition, diversity indices, and species cooccurrence were compared between groups. Random forest and receiver operating characteristic analysis were used to identify potential diagnostic biomarkers. Relationships between discriminant bacteria and poststroke functional outcomes were estimated.

Results: Higher alpha diversity of gut microbiota was observed in poststroke patients as compared to the healthy controls (p < 0.05). Beta diversity showed that microbiota composition in the poststroke group was significantly different from that in the control group. Relative abundance of nine genera increased significantly in poststroke patients, while 82 genera significantly decreased (p < 0.05). The accuracy, specificity, and susceptibility of the optimal model consisted of the top 10 discriminant species were 93%, 100%, and 86%, respectively. Subgroup analysis showed that bacterial taxa abundant between subacute and chronic stroke patients were overall different (p < 0.05). The modified Rankin scale (mRS) (r = -0.370, p < 0.05), Fugl-Meyer assessment (FMA) score (r = 0.364, p < 0.05), water swallow test (WST) (r = 0.340, p < 0.05), and Barthel index (BI) (r = 0.349, p < 0.05) were significantly associated with alterations of distinctive gut microbiota.

Conclusions: The gut microbiota in patients with stroke was significantly changed in terms of richness and composition. Significant associations were detected between alterations of distinctive gut microbiota and global functional prognosis. It would facilitate novel treatment target selection in the context of stroke while the causal relationships between distinctive gut microbiota alterations and functional variations need to be further verified with well-designed studies.

Purpose: This study is aimed at exploring how soleus H-reflex change in poststroke patients with spasticity influenced by body position.

Materials and methods: Twenty-four stroke patients with spastic hemiplegia and twelve age-matched healthy controls were investigated. Maximal Hoffmann-reflex (Hmax) and motor potential (Mmax) were elicited at the popliteal fossa in both prone and standing positions, respectively, and the Hmax/Mmax ratio at each body position was determined. Compare changes in reflex behavior in both spastic and contralateral muscles of stroke survivors in prone and standing positions, and match healthy subjects in the same position.

Results: In healthy subjects, Hmax and Hmax/Mmax ratios were significantly decreased in the standing position compared to the prone position (Hmax: p = 0.000, Hmax/Mmax: p = 0.016). However, Hmax/Mmax ratios were increased in standing position on both sides in poststroke patients with spasticity (unaffected side: p = 0.006, affected side: p = 0.095). The Hmax and Hmax/Mmax ratios were significantly more increased on the affected side than unaffected side irrespective of the position.

Conclusions: The motor neuron excitability of both sides was not suppressed but instead upregulated in the standing position in subjects with spasticity, which may suggest that there was abnormal regulation of the Ia pathway on both sides.