Neural Plasticity最新文献

Hippocampal neuronal damage likely underlies cognitive impairment in vascular dementia (VaD). PPARγ coactivator-1α (PGC-1α) is a master regulator of mitochondrial biogenesis. However, the role and the precise mechanism of how PGC-1α alleviates hippocampal neuronal injury remain unknown. To address this question, HT-22 cells, an immortalized hippocampal neuron cell line, with or without PGC-1α overexpression were subjected to oxygen-glucose deprivation (OGD), which mimics the circumstance of chronic cerebral hypoperfusion in VaD. After OGD, cell viability was assessed using the MTS assay. The mitochondrial function and reactive oxygen species (ROS) were both detected. ChIP-Seq analysis was employed to discover the underlying molecular mechanism of PGC-1α-mediated neuroprotective effects. Our results showed that mitochondrial membrane potentials were increased and ROS production was decreased in PGC-1α overexpressing cells, which increased cell viability. The further bioinformatics analysis from ChIP-Seq data indicated that PGC-1α may participate in the regulation of apoptosis, autophagy, and mitophagy pathways in HT-22 cells. We found that PGC-1α promoted the LC3-II formation and reduced the neuronal apoptosis determined by TUNEL staining. In addition, PGC-1α upregulated the expressions of mitochondrial antioxidants, including SOD2, Trx2, and Prx3. In summary, our findings indicate that PGC-1α may attenuate OGD-induced hippocampal neuronal damage by regulating multiple mechanisms, like autophagy and mitochondrial function. Thus, PGC-1α may be a potential therapeutic target for hippocampal damage associated with cognitive impairment.

The analysis of structural covariance has emerged as a powerful tool to explore the morphometric correlations among broadly distributed brain regions. However, little is known about the interactions between the damaged primary motor cortex (M1) and other brain regions in stroke patients with motor deficits. This study is aimed at investigating the structural covariance pattern of the ipsilesional M1 in chronic subcortical stroke patients with motor deficits. High-resolution T1-weighted brain images were acquired from 58 chronic subcortical stroke patients with motor deficits (29 with left-sided lesions and 29 with right-sided lesions) and 50 healthy controls. Structural covariance patterns were identified by a seed-based structural covariance method based on gray matter (GM) volume. Group comparisons between stroke patients (left-sided or right-sided groups) and healthy controls were determined by a permutation test. The association between alterations in the regional GM volume and motor recovery after stroke was investigated by a multivariate regression approach. Structural covariance analysis revealed an extensive increase in the structural interactions between the ipsilesional M1 and other brain regions in stroke patients, involving not only motor-related brain regions but also non-motor-related brain regions. We also identified a slightly different pattern of structural covariance between the left-sided stroke group and the right-sided stroke group, thus indicating a lesion-side effect of cortical reorganization after stroke. Moreover, alterations in the GM volume of structural covariance brain regions were significantly correlated to the motor function scores in stroke patients. These findings indicated that the structural covariance patterns of the ipsilesional M1 in chronic subcortical stroke patients were induced by motor-related plasticity. Our findings may help us to better understand the neurobiological mechanisms of motor impairment and recovery in patients with subcortical stroke from different perspectives.

Background: Tai chi (TC) has received increased attention in stroke rehabilitation, yet services are greatly underutilized. An increasing number of systematic reviews and meta-analyses (SRs/MAs) have begun to investigate the effects of TC on balance function in stroke patients. The aim of this current study was to systematically collate, appraise, and synthesize the results of these SRs/MAs using a systematic overview.

Methods: Eight databases were searched: PubMed, Cochrane Library, Embase, Web of Science, CNKI, SinoMed, Chongqing VIP, and Wanfang Data. SRs/MAs of TC on balance function in stroke patients were included. Literature selection, data extraction, and assessment of the review quality were performed by two independent reviewers. Methodological quality was assessed by the Assessing the Methodological Quality of Systematic Reviews 2 (AMSTAR-2), reporting quality by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), and evidence quality by Grading of Recommendations, Assessment, Development, and Evaluation (GRADE).

Results: Nine SRs/MAs were included in this study. For methodological quality, what resulted in unsatisfactory methodological quality was noncompliance with critical item 4 (using a comprehensive literature search strategy) and critical item 7 (providing the list of excluded research literature). For reporting quality, what resulted in unsatisfactory reporting quality was inadequate reporting of Q1 (protocol and registration), Q8 (search), Q15 (risk of bias across studies), Q16 (additional analyses), Q22 (risk of bias across studies), Q23 (additional analysis), and Q27 (funding). For GRADE, the evidence quality was high in 0, moderate in 3, low in 11, and very low in 6. Risk of bias was the most common factor leading to downgrading of evidence, followed by inconsistency, imprecision, publication bias, and indirectness.

Conclusions: TC may have beneficial effects on balance function in stroke survivors; however, this finding is limited by the generally low methodology, reporting quality, and evidence quality for published SRs/MAs.

Ischemic stroke and traumatic brain injury (TBI) are among the leading causes of death and disability worldwide with impairments ranging from mild to severe. Many therapies are aimed at improving functional and cognitive recovery by targeting neural repair but have encountered issues involving efficacy and drug delivery. As a result, therapeutic options for patients are sparse. Neurotrophic factors are one of the key mediators of neural plasticity and functional recovery. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) serve as potential therapeutic options to increase neural repair and recovery as they promote neuroprotection and regeneration. BDNF and NGF have demonstrated the ability to improve functional recovery in preclinical and to a lesser extent clinical studies. Direct and indirect methods to increase levels of neurotrophic factors in animal models have been successful in improving postinjury outcome measures. However, the translation of these studies into clinical trials has been limited. Preclinical experiments have largely failed to result in significant impacts in clinical research. This review will focus on the administration of these neurotrophic factors in preclinical and clinical stroke and TBI and the challenges in translating these therapies from the bench to the clinic.

Chronic pain patients often develop mental disorders, and anxiety disorders are common. We hypothesize that the comorbid anxiety results from an imbalance between the reward and antireward system due to persistent pain, which leads to the dysfunction of the pain and anxiety regulatory system. In this review, we will focus on changes in neuroplasticity, especially in neural circuits, during chronic pain and anxiety as observed in animal studies. Several neural circuits within specific regions of the brain, including the nucleus accumbens, lateral habenular, parabrachial nucleus, medial septum, anterior cingulate cortex, amygdala, hippocampus, medial prefrontal cortex, and bed nucleus of the stria terminalis, will be discussed based on novel findings after chemogenetic or optogenetic manipulation. We believe that these animal studies provide novel insights into human conditions and can guide clinical practice.

Spike-timing-dependent long-term depression (t-LTD) of glutamatergic layer (L)4-L2/3 synapses in developing neocortex requires activation of astrocytes by endocannabinoids (eCBs), which release glutamate onto presynaptic NMDA receptors (preNMDARs). The exact function of preNMDARs in this context is still elusive and strongly debated. To elucidate their function, we show that bath application of the eCB 2-arachidonylglycerol (2-AG) induces a preNMDAR-dependent form of chemically induced LTD (eCB-LTD) in L2/3 pyramidal neurons in the juvenile somatosensory cortex of rats. Presynaptic Ca²⁺ imaging from L4 spiny stellate axons revealed that action potential (AP) evoked Ca²⁺ transients show a preNMDAR-dependent broadening during eCB-LTD induction. However, blockade of voltage-dependent Ca²⁺ channels (VDCCs) did not uncover direct preNMDAR-mediated Ca²⁺ transients in the axon. This suggests that astrocyte-mediated glutamate release onto preNMDARs does not result in a direct Ca²⁺ influx, but that it instead leads to an indirect interaction with presynaptic VDCCs, boosting axonal Ca²⁺ influx. These results reveal one of the main remaining missing pieces in the signaling cascade of t-LTD at developing cortical synapses.

The aim of this study was to investigate the effect of the P2Y2 receptor (P2Y2R) signaling pathway on neuronal regeneration and angiogenesis during spinal cord injury (SCI). The rats were randomly divided into 3 groups, including the sham+dimethyl sulfoxide (DMSO), SCI+DMSO, and SCI+P2Y2R groups. The SCI animal models were constructed. A locomotor rating scale was used for behavioral assessments. The apoptosis of spinal cord tissues was detected by TUNEL staining. The expression levels of P2Y2R, GFAP, nestin, Tuj1, and CD34 were detected by immunofluorescence staining, and the expression levels of TNF-α, IL-1β, and IL-6 were detected by enzyme-linked immunosorbent assay. The locomotor score in the model group was significantly lower than the sham group. The expression of P2Y2R was increased after SCI. The expression levels of TNF-α, IL-1β, and IL-6 were increased remarkably in the SCI model group compared with the sham group. The P2Y2R inhibitor relieved neuronal inflammation after SCI. Compared with the sham group, the apoptotic rate of spinal cord tissue cells in the model group was significantly increased. The P2Y2R inhibitor reduced the apoptosis of the spinal cord tissue. The expressions of CD34, Tuj1, and nestin in the model group were decreased, while the expressions of GFAP and P2Y2R were increased. The P2Y2R inhibitor reversed their expression levels. The P2Y2R inhibitor could alleviate SCI by relieving the neuronal inflammation, inhibiting the spinal cord tissue apoptosis, and promoting neuronal differentiation and vascular proliferation after SCI. P2Y2R may serve as a target for the treatment of SCI.

Temporal interference (TI) could stimulate deep motor cortex and induce movement without affecting the overlying cortex in previous mouse studies. However, there is still lack of evidence on potential TI effects in human studies. To fill this gap, we collected resting-state functional magnetic resonance imaging data on 40 healthy young participants both before and during TI stimulation on the left primary motor cortex (M1). We also chose a widely used simulation approach (tDCS) as a baseline condition. In the stimulation session, participants were randomly allocated to 2 mA TI or tDCS for 20 minutes. We used a seed-based whole brain correlation analysis method to quantify the strength of functional connectivity among different brain regions. Our results showed that both TI and tDCS significantly boosted functional connection strength between M1 and secondary motor cortex (premotor cortex and supplementary motor cortex). This is the first time to demonstrate substantial stimulation effect of TI in the human brain.

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.