Neural Plasticity最新文献

An improvement in the activities of daily living (ADLs) is significantly related to the quality of life and prognoses of patients with stroke. However, the factors predicting significant improvement in ADL (SI-ADL) have not yet been clarified. Therefore, we sought to identify the key factors affecting SI-ADL in patients with stroke after rehabilitation therapy using both logistic regression modeling and decision tree modeling. We retrospectively collected and analyzed the clinical data of 190 patients with stroke who underwent rehabilitation therapy at our hospital between January 2020 and July 2020. General and rehabilitation therapy data were extracted, and the Barthel index (BI) score was used for outcome assessment. We defined SI-ADL as an improvement in the BI score by 15 points or more during hospitalization. Logistic regression and decision tree models were established to explore the SI-ADL predictors. We then used receiver operating characteristic (ROC) curves to compare the logistic regression and decision tree models. Univariate analysis revealed that compared with the non-SI-ADL group, the SI-ADL group showed a significantly shorter course of stroke, longer hospital stay, and higher rate of receiving occupational and speech therapies (all P < 0.05). Binary logistic regression analysis revealed the course of stroke at admission (odds ratio (OR) = 0.986, 95%confidence interval (CI) = 0.979-0.993; P < 0.001) and the length of hospital stay (OR = 1.030, 95%CI = 1.013-1.047; P =0.001) as the independent predictors of SI-ADL. ROC comparisons revealed no significant differences in the areas under the curves for the logistic regression and decision tree models (0.808 vs. 0.831; z = 0.977, P = 0.329). Both models identified the course of disease at admission and the length of hospital stay as key factors affecting SI-ADL. Early initiation of rehabilitation therapy is of immense importance for improving the ADLs in patients with stroke.

Objective: The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS).

Methods: In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p < 0.01 and cluster p < 0.05) correction was applied. The correlation analyses were performed between clinical scores and altered metrics values.

Results: Compared to HCs, patients with acute BGIS showed decreased ALFF in the right supramarginal gyrus (SMG) in the conventional and slow-4 bands, increased fALFF in the right middle frontal gyrus (MFG) in the conventional and slow-4 bands, and increased fALFF in the bilateral caudate in the slow-5 frequency band. The fALFF value of the right caudate in the slow-5 frequency band was negatively correlated with the clinical scores.

Conclusion: In conclusion, this study showed the alterations in ALFF and fALFF in three frequency bands between patients with acute BGIS and HCs. The results reflected that the abnormal LFO amplitude might be related with different frequency bands and promoted our understanding of pathophysiological mechanism in acute BGIS.

Background: Impaired cognitive ability to anticipate the required control for an upcoming task in patients with stroke may affect rehabilitation outcome. The cortical excitability of task-related motor anticipation for upper limb movement induced by virtual reality (VR) training remains unclear.

Aims: To investigate the effect of VR training on the cortical excitability of motor anticipation when executing upper limb movement in patients with subacute stroke.

Methods: A total of thirty-six stroke survivors with upper limb hemiparesis resulting from the first occurrence of stroke within 1 to 3 months were recruited. Participants were randomly allocated to the VR intervention group or conventional therapy group. Event-related potentials (ERPs) and electromyography (EMG) were used to simultaneously record the cortical excitability and muscle activities during palmar grasp motion. Outcome measures of the contingent negative variation (CNV) latency and amplitude, EMG reaction time, Upper Limb Fugl-Meyer Assessment (UL-FMA), Action Research Arm Test (ARAT), and National Institutes of Health Stroke Scale (NIHSS) were recorded pre- and postintervention. The between-group difference was analysed by mixed model ANOVA.

Results: The EMG onset time of the paretic hand in the VR group was earlier than that observed in the control group (t = 2.174, p = 0.039) postintervention. CNV latency reduction postintervention was larger in the VR group than in the control group (t = 2.411, p = 0.021) during paretic hand movement. The reduction in CNV amplitude in the VR group was larger in the VR group than in the control group (p < 0.001 for all electrodes except for C3) when executing paretic hand movement. ARAT and UL-FMA scores were significantly higher in the VR group than in the control group (p = 0.019 and p = 0.037, respectively) postintervention. No significant difference in the reduction in NIHSS was found between the VR and control groups (p = 0.072).

Conclusions: VR intervention is superior to conventional therapy to improve the cognitive neural process of motor anticipation and reduce the excessive compensatory activation of the contralesional hemisphere. The improvements observed in the cognitive neural process corroborated with the improvements in hand function.

Objective: Volume reduction and structural abnormality is the most replicated finding in neuroimaging studies of Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is the early stage of AD development. Thus, it is necessary to investigate the link between atrophy of regions of interest (ROIs) in medial temporal lobe, the variation trend of ROI densities and volumes among patients with cognitive impairment, and the distribution characteristics of ROIs in the aMCI group, Alzheimer's disease (AD) group, and normal control (NC) group.

Methods: 30 patients with aMCI, 16 patients with AD, and 30 NC are recruited; magnetic resonance imaging (MRI) brain scans are conducted. Voxel-based morphometry was employed to conduct the quantitative measurement of gray matter densities of the hippocampus, amygdala, entorhinal cortex, and mammillary body (MB). FreeSurfer was utilized to automatically segment the hippocampus into 21 subregions and the amygdala into 9 subregions. Then, their subregion volumes and total volume were calculated. Finally, the ANOVA and multiple comparisons were performed on the above-mentioned data from these three groups.

Results: AD had lower GM densities than MCI, and MCI had lower GM densities than NC, but not all of the differences were statistically significant. In the comparisons of AD-aMCI-NC, AD-aMCI, and AD-NC, the hippocampus, amygdala, and entorhinal cortex showed differences in the gray matter densities (p < 0.05); the differences of mammillary body densities were not significant in the random comparison between these three groups (p > 0.05). The hippocampus densities and volumes of the subjects from the aMCI group and the AD group were bilaterally symmetric. The gray matter densities of the right side of the entorhinal cortex inside each group and the hippocampus from the NC group were higher than those of the left side (p < 0.05), and the gray matter densities of the amygdala and mammillary body were bilaterally symmetric in the three groups (p > 0.05). There were no gender differences of four ROIs in the AD, aMCI, and NC groups (p > 0.05). The volume differences of the hippocampus presubiculum-body and parasubiculum manifest no statistical significance (p > 0.05) in the random comparison between these three groups. Volume differences of the left amygdala basal nucleus, the left lateral nucleus, the left cortical amygdala transitional area, the left paravamnion nucleus, and bilateral hippocampal amygdala transition area (HATA) had statistical differences only between the AD group and the NC group (p < 0.05).

Conclusion: Structural defects of medial temporal lobe subfields were revealed in the aMCI and AD groups. Decreased gray matter densities of the hippocampus, entorhinal cortex, and amygdala could distinguish patients with early stage of AD between aMCI and NC. Volume d

Background: The aim was to investigate the influence of propionic acid (PA) on the endoplasmic reticulum (ER), unfolded protein response (UPR) state, and astrocyte/microglia markers in rat ventromedial hypothalamus (VMH) after type 2 diabetes mellitus (T2DM).

Methods: Male Wistar rats were divided: (1) control, (2) T2DM, and groups that received the following (14 days, orally): (3) metformin (60 mg/kg), (4) PA (60 mg/kg), and (5) PA+metformin. Western blotting, RT-PCR, transmission electron microscopy, and immunohistochemical staining were performed.

Results: We found T2DM-associated enlargement of ER cisterns, while drug administration slightly improved VMH ultrastructural signs of damage. GRP78 level was 2.1-fold lower in T2DM vs. control. Metformin restored GRP78 to control, while PA increased it by 2.56-fold and metformin+PA-by 3.28-fold vs. T2DM. PERK was elevated by 3.61-fold in T2DM, after metformin-by 4.98-fold, PA-5.64-fold, and metformin+PA-3.01-fold vs. control. A 2.45-fold increase in ATF6 was observed in T2DM. Metformin decreased ATF6 content vs. T2DM. Interestingly, PA exerted a more pronounced lowering effect on ATF6, while combined treatment restored ATF6 to control. IRE1 increased in T2DM (2.4-fold), metformin (1.99-fold), and PA (1.45-fold) groups vs. control, while metformin+PA fully normalized its content. The Iba1 level was upregulated in T2DM (5.44-fold) and metformin groups (6.88-fold). Despite PA treatment leading to a further 8.9-fold Iba1 elevation, PA+metformin caused the Iba1 decline vs. metformin and PA treatment. GFAP level did not change in T2DM but rose in metformin and PA groups vs. control. PA+metformin administration diminished GFAP vs. PA. T2DM-induced changes were associated with dramatically decreased ZO-1 levels, while PA treatment increased it almost to control values.

Conclusions: T2DM-induced UPR imbalance, activation of microglia, and impairments in cell integrity may trigger VMH dysfunction. Drug administration slightly improved ultrastructural changes in VMH, normalized UPR, and caused an astrocyte activation. PA and metformin exerted beneficial effects for counteracting diabetes-induced ER stress in VMH.

Sensorineural hearing loss (SNHL) is one of the most common causes of disability worldwide. Previous evidence suggests that reactive oxygen species (ROS) may play an important role in the occurrence and development of SNHL, while its mechanism remains unclear. We cultured dissected organs of Corti in medium containing different concentrations (0, 0.25, 0.5, 0.75, 1, and 1.25 mM) of hydrogen peroxide (H₂O₂) and established a four-concentration model of 0, 0.5, 0.75, and 1 mM to study different degrees of damage. We examined ROS-induced mitochondrial damage and the role of sirtuin 3 (SIRT3). Our results revealed that the number of ribbon synapses and hair cells appeared significantly concentration-dependent decrease with exposure to H₂O₂. Outer hair cells (OHCs) and inner hair cells (IHCs) began to be lost, and activation of apoptosis of hair cells (HCs) was observed at 0.75 mM and 1 mM H₂O₂, respectively. In contrast with the control group, the accumulation of ROS was significantly higher, and the mitochondrial membrane potential (MMP) was lower in the H₂O₂-treated groups. Furthermore, the expression of SIRT3, FOXO3A, and SOD2 proteins declined, except for an initial elevation of SIRT3 between 0 and 0.75 mM H₂O₂. Administration of the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine resulted in increased damage to the cochlea, including loss of ribbon synapses and hair cells, apoptosis of hair cells, more production of ROS, and reduced mitochondrial membrane potential. Thoroughly, our results highlight that ROS-induced mitochondrial oxidative damage drives hair cell degeneration and apoptosis. Furthermore, SIRT3 is crucial for preserving mitochondrial function and protecting the cochlea from oxidative damage and may represent a possible therapeutic target for SNHL.

Proprioceptive deficit is one of the common sensory impairments following stroke and has a negative impact on motor performance. However, evidence-based training procedures and cost-efficient training setups for patients with poststroke are still limited. We compared the effects of proprioceptive training versus nonspecific sensory stimulation on upper limb proprioception and motor function rehabilitation. In this multicenter, single-blind, randomized controlled trial, 40 participants with poststroke hemiparesis were enrolled from 3 hospitals in China. Participants were assigned randomly to receive proprioceptive training involving passive and active movements with visual feedback (proprioceptive training group [PG]; n = 20) or nonspecific sensory stimulation (control group [CG]; n = 20) 20 times in four weeks. Each session lasted 30 minutes. A clinical assessor blinded to group assignment evaluated patients before and after the intervention. The primary outcome was the change in the motor subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-M). Secondary outcomes were changes in box and block test (BBT), thumb localization test (TLT), the sensory subscale of the Fugl-Meyer assessment for upper extremity (FMA-UE-S), and Barthel Index (BI). The results showed that the mean change scores of FMA-UE were significantly greater in the PG than in the CG (p = 0.010 for FMA-UE-M, p = 0.033 for FMA-UE-S). The PG group was improved significantly in TLT (p = 0.010) and BBT (p = 0.027), while there was no significant improvement in TLT (p = 0.083) and BBT (p = 0.107) for the CG group. The results showed that proprioceptive training was effective in improving proprioception and motor function of the upper extremity in patients with poststroke. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2000037808).

The mammalian hippocampal dentate gyrus is a niche for adult neurogenesis from neural stem cells. Newborn neurons integrate into existing neuronal networks, where they play a key role in hippocampal functions, including learning and memory. In the ageing brain, neurogenic capability progressively declines while in parallel increases the risk for developing Alzheimer's disease (AD), the main neurodegenerative disorder associated with memory loss. Numerous studies have investigated whether impaired adult neurogenesis contributes to memory decline in AD. Here, we review the literature on adult hippocampal neurogenesis (AHN) and AD by focusing on both human and mouse model studies. First, we describe key steps of AHN, report recent evidence of this phenomenon in humans, and describe the specific contribution of newborn neurons to memory, as evinced by animal studies. Next, we review articles investigating AHN in AD patients and critically examine the discrepancies among different studies over the last two decades. Also, we summarize researches investigating AHN in AD mouse models, and from these studies, we extrapolate the contribution of molecular factors linking AD-related changes to impaired neurogenesis. Lastly, we examine animal studies that link impaired neurogenesis to specific memory dysfunctions in AD and review treatments that have the potential to rescue memory capacities in AD by stimulating AHN.

Alzheimer's disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb-Gastrodia elata-and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aβ _1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aβ, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.

Background: Contralaterally controlled neuromuscular electrical stimulation (CCNMES) is a novel electrical stimulation treatment for stroke; however, reports on the efficacy of CCNMES on lower extremity function after stroke are scarce.

Objective: To compare the effects of CCNMES versus NMES on lower extremity function and activities of daily living (ADL) in subacute stroke patients.

Methods: Forty-four patients with a history of subacute stroke were randomly assigned to a CCNMES group and a NMES group (n = 22 per group). Twenty-one patients in each group completed the study per protocol, with one subject lost in follow-up in each group. The CCNMES group received CCNMES to the tibialis anterior (TA) and the peroneus longus and brevis muscles to induce ankle dorsiflexion motion, whereas the NMES group received NMES. The stimulus current was a biphasic waveform with a pulse duration of 200 μs and a frequency of 60 Hz. Patients in both groups underwent five 15 min sessions of electrical stimulation per week for three weeks. Indicators of motor function and ADL were measured pre- and posttreatment, including the Fugl-Meyer assessment of the lower extremity (FMA-LE) and modified Barthel index (MBI). Surface electromyography (sEMG) assessments included average electromyography (aEMG), integrated electromyography (iEMG), and root mean square (RMS) of the paretic TA muscle.

Results: Values for the FMA-LE, MBI, aEMG, iEMG, and RMS of the affected TA muscle were significantly increased in both groups after treatment (p < 0.01). Patients in the CCNMES group showed significant improvements in all the measurements compared with the NMES group after treatment. Within-group differences in all post- and pretreatment indicators were significantly greater in the CCNMES group than in the NMES group (p < 0.05).

Conclusion: CCNMES improved motor function and ADL ability to a greater extent than the conventional NMES in subacute stroke patients.