Neuroreport最新文献

Objective: This study explores the changes in functional connectivity density (FCD) among patients with diabetic retinopathy and its associations with gene expression and the distribution of neurotransmitter density, aiming to elucidate potential pathophysiological mechanisms underlying diabetic retinopathy.

Methods: This study investigates changes in short-range functional connectivity density (sFCD) within regions and long-range functional connectivity density (lFCD) between regions in 46 patients with diabetic retinopathy compared with 46 healthy controls. In addition, we examine the relationship between FCD changes in patients with diabetic retinopathy and whole-brain gene expression through partial least squares (PLS) regression and functional enrichment analysis of PLS-weighted genes. Finally, we assess the spatial correlation between abnormal FCD patterns and neurotransmitter density distribution using correlation analysis.

Results: The patients with diabetic retinopathy show a reduction in lFCD in the left inferior occipital gyrus and in the cortex surrounding the left calcarine fissure (left Cal) and a significant decrease in sFCD in the left Cal and the supplementary motor area (SMA). Furthermore, FCD is significantly positively correlated with the PLS1 gene and exhibits notable associations with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the abnormal FCD patterns in patients with diabetic retinopathy demonstrate a significant spatial correlation with the density of 5HT1A and CB1 receptors.

Conclusion: In summary, patients with diabetic retinopathy have different degrees of abnormal brain connectivity function in vision-related and SMA regions, and this abnormal performance may be related to the high oxidative stress state and neurovascular abnormalities present in patients with diabetic retinopathy.

Objective: To investigate gray-white matter injury in heatstroke using multimodal MRI, and precisely localize damaged white matter segments via automated fiber quantification (AFQ) with clinical correlation.

Results: Compared with the healthy control group, VBM revealed reduced volume in bilateral cerebellar anterior lobes and left fusiform gyrus. TBSS showed widespread white matter abnormalities. AFQ identified: (a) Decreased fractional anisotropy in left corticospinal tract and right inferior fronto-occipital fasciculus; (b) increased mean diffusivity in left thalamic radiation, bilateral corticospinal tracts, corpus callosum forceps minor, bilateral inferior fronto-occipital fasciculus, left inferior longitudinal fasciculus, right superior longitudinal fasciculus, and bilateral uncinate fasciculi (false discovery rate - P  < 0.05). Specific nodes in the left thalamic radiation, right corticospinal tract, right inferior fronto-occipital fasciculus, left inferior longitudinal fasciculus, and left uncinate fasciculus were correlated with Glasgow Coma Scale and coagulopathy markers.

Conclusion: Heatstroke involves cerebellar/cortical atrophy and segment-specific white matter damage, where AFQ-precise localization links microstructural alterations to clinical severity and coagulopathy.

Objective: This study investigated whether parameter-optimized paired associative stimulation (PAS) could enhance neurological recovery after cerebral ischemia by modulating oxidative stress and inflammation in a rat middle cerebral artery occlusion (MCAO) model.

Methods: Twenty-four Sprague-Dawley rats were randomly divided into Sham, Model, PAS-ISI-10 ms, and PAS-ISI-15 ms groups. The MCAO model was established using the intraluminal filament method. PAS intervention (90 paired pulses/day for 28 days) was initiated 24 h postischemia. Neurological function was assessed using Longa scores, grip strength, and corner tests. Cerebral infarction (TTC staining), neuronal survival (Nissl staining), apoptosis (TUNEL), neuroregeneration markers (GAP43, BDNF, MAP2, and Syn), oxidative stress (GSH-Px and MDA), and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were evaluated.

Results: The PAS-ISI-10 ms group demonstrated significantly better neurological recovery than PAS-ISI-15 ms ( P  < 0.05), with reduced infarct volume ( P  < 0.01) and lower apoptosis rates ( P  < 0.01). Neuroregenerative markers showed greater upregulation in the 10 ms group ( P  < 0.05). Oxidative stress markers were significantly improved in PAS groups (GSH-Px increased P  < 0.01; MDA decreased P  < 0.01), with more pronounced effects in the 10ms condition. Proinflammatory cytokines were markedly reduced in both PAS groups ( P  < 0.05), showing stronger suppression in the 10ms group.

Conclusion: Parameter-optimized PAS with 10-ms ISI promotes neurological recovery after cerebral ischemia through coordinated antioxidant, anti-inflammatory, and neuroregenerative mechanisms. These findings provide evidence for optimizing noninvasive neuromodulation strategies in stroke rehabilitation.

Background: Emerging evidence suggests that blood-oxygen-level-dependent signals in white matter reflect functional activity; however, it remains unclear whether white matter function is altered in rhegmatogenous retinal detachment (RRD) and how it interacts with gray matter.

Methods: We conducted resting-state functional MRI analyses in patients with RRD and healthy controls to investigate regional white matter activity using amplitude of low-frequency fluctuations/fractional ALFF (ALFF/fALFF), and cross-tissue white matter-gray matter functional connectivity. Voxel-wise analyses were performed to identify aberrant white matter regions, and seed-based connectivity mapping was applied using affected white matter tracts. Support vector machine models were constructed to evaluate the diagnostic utility of these functional features.

Results: Patients with RRD exhibited significantly increased ALFF/fALFF in key projection fibers, including the bilateral anterior corona radiata (ACR) and anterior limb of the internal capsule (ALIC). Enhanced functional connectivity was observed between the left ACR and nonvisual gray matter regions such as the right middle temporal gyrus and medial orbitofrontal cortex. Among all features, the fALFF value of the left ALIC demonstrated the highest classification performance (area under the curve = 0.8974) in distinguishing RRD from healthy controls.

Conclusion: These findings reveal aberrant spontaneous low-frequency oscillatory activity and enhanced white matter-gray matter coupling in patients with RRD, reflecting cross-tissue functional reorganization beyond the retina. Notably, the elevated fALFF signal in the left ALIC demonstrates strong potential as a neuroimaging biomarker. This study underscores the value of white matter functional metrics in characterizing central nervous system alterations in RRD and offers novel insights into its neurobiological underpinnings.

Background: Mild traumatic brain injury (mTBI) commonly has long-term cognitive and functional consequences; however, it is not clear whether these adverse outcomes begin in the acute phase of mTBI and are associated with changes in brain morphology and function.

Methods: The current study used T1-weighted MRI to determine whether cortical thickness, gray matter volume (GMV), and morphological brain networks were altered in patients with mTBI within 7 days of injury, and to examine whether these changes were associated with postacute cognitive and emotional abnormalities. Adults aged 18-56 years with mTBI ( n  = 43) and healthy controls ( n  = 37) completed the cognitive, emotional evaluation, and MRI examination, during which patients with mTBI completed symptom reports. Cortical thickness and GMV were estimated using Computational Anatomy Toolbox 12. On this basis, a gray matter covariance network was constructed based on the cortical thickness.

Results: After false discovery rate (FDR) correction, groups differed significantly on the left parahippocampal gyrus and left orbital part of the superior frontal gyrus GMV (mTBI > controls), but no cortical thickness. The network topological properties were also changed in the acute stage of mTBI. The GMV abnormality was related to postacute cognitive and emotional changes in the mTBI group.

Conclusion: The results emphasize that adverse outcomes begin in the acute phase and that the left parahippocampal gyrus and left orbital part of the superior frontal gyrus and related brain network abnormalities may be potential neuroimaging biomarkers explaining acute cognitive and depressive symptoms.

Purpose of the research: This study aimed to explore the effects of exercise on sensorimotor recovery after stroke, neuroplasticity changes in the brain and spinal cord, and spinal cord compensation mechanisms.

Methods: A rat model of ischemic stroke was induced using the middle cerebral artery occlusion/reperfusion method. A T10 spinal cord injury (SCI) model was induced using a modified Allen procedure. The animals were randomly assigned into: Sham group (S), stroke group (M), stroke+SCI group (MS), stroke+exercise+SCI group (MSI), and stroke+SCI group (MI). Neurological function was assessed poststroke using the modified Neurological Severity Score (mNSS) and Garcia scores. Infarct volumes were evaluated using triphenyl tetrazolium chloride staining, and neuronal damage was assessed using Nissl staining. Tumor necrosis factor-α (TNF-α), interleukin (IL)-10, and IL-1β levels were measured using ELISA. Neuroplasticity markers [GAP43, PSD-95, synapsin I, and brain-derived neurotrophic factor (BDNF)] levels were analyzed using WB, IHC, and ELISA.

Results: Exercise improved neurological function in stroke rats, as evidenced by the enhanced mNSS and Garcia scores in the MS group compared to the M group. Exercise also alleviated neuronal damage, with the MS group showing higher neuron counts and more intact Nissl bodies than the M group. Exercise in the MS group downregulated inflammation (TNF-α down, IL-10 up) compared to the M group. Furthermore, exercise upregulated neuroplasticity markers and BDNF in both the brain and spinal cord. The beneficial effects of exercise on neurological recovery were diminished in the presence of SCI, as evidenced by the impaired recovery in the MSI group.

Conclusions: Exercise enhances stroke recovery by improving neuroplasticity, reducing inflammation, and highlighting the spinal cord's role in compensation. These findings suggest spinal cord-targeted therapies may improve rehabilitation outcomes.

Background: Subarachnoid hemorrhage (SAH) is a cerebrovascular disease with a very high disability and mortality rate, which brings a huge economic burden to society. It is reported that inhibition of forkhead box O3 (FOXO3) can alleviate brain edema and neuroinflammation after SAH. However, the role and mechanism of FOXO3 in regulating SAH progression need to be further studied.

Methods: Mouse microglia were treated with oxyhemoglobin (OxyHb) to build SAH cell model in vitro. Western blot was used to measure the protein levels of FOXO3, ubiquitin-specific peptidase 30 (USP30), embryonic lethal-abnormal vision like protein 1 (ELAVL1), and pyroptosis-related proteins. Cell proliferation was tested by cell counting kit 8 assay and 5-ethynyl-2' -deoxyuridine assay. Inflammatory factors were detected by ELISA, and cell polarization was evaluated using flow cytometry. Cell pyroptosis was assessed by detecting. Co-immunoprecipitation assay, immunofluorescence colocalization assay, and RNA immunoprecipitation assay were used to evaluate the interaction between FOXO3 and USP30 or ELAVL1.

Results: Downregulation of FOXO3 inhibited inflammation, M1 polarization, and pyroptosis in OxyHb-induced microglia. USP30 promoted FOXO3 expression through deubiquitination. USP30 knockdown suppressed inflammation, M1 polarization, and pyroptosis in OxyHb-induced microglia, and these effects were abolished by FOXO3 overexpression. Also, ELAVL1 interacted with FOXO3 to facilitate its mRNA stability. Meanwhile, USP30 increased FOXO3 expression to activate the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway.

Conclusion: USP30-mediated deubiquitination of FOXO3 contributed to OxyHb-induced microglia inflammation, M1 polarization, and pyroptosis, providing a novel target for the treatment of SAH.

Objective: This study seeks to investigate the roles and underlying mechanisms of cell cycle exit and neuronal differentiation 1 (CEND1) on Parkinson's disease.

Methods: Real-time quantitative PCR (RT-qPCR) was employed to assess the expression levels of CEND1 in peripheral blood samples of Parkinson's patients. A cell model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPP + )-induced Parkinson's disease was established in-vitro. 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assays were used to evaluate the impact of CEND1 on the viability of SH-SY5Y cells induced by MPP + , while flow cytometry was used to assess apoptosis of these cells. The expression of oxidative stress and inflammatory factors in MPP + -treated cells was detected by ELISA. In addition, the effect of CEND1 on Parkinson's disease was interfered by an activator of the nuclear factor kappa B (NF-κB) pathway to clarify the relationship between CEND1 and the NF-κB pathway in a cell model of Parkinson's disease.

Results: CEND1 expression is markedly downregulated in patients with Parkinson's disease and cells of the Parkinson's disease model. Downregulation of CEND1-induced apoptosis, inhibited cell proliferation, and promoted expression of inflammatory factors in MPP + -treated cells; however, high expression of CEND1 inhibited MPP + -induced apoptosis, inflammatory factor release, and oxidative stress. In addition, CEND1 inhibited the activation of the NF-κB pathway induced by MPP + , and phorbol 12-myristate 13-acetate reversed the effect of CEND1 on Parkinson's disease.

Conclusion: CEND1 plays a protective role in the Parkinson's disease cell model by suppressing NF-κB signaling pathway activation, offering a potential target and foundation for the diagnosis and therapy of Parkinson's disease.

Objective: Microglia can be polarized into a proinflammatory M1 phenotype or an anti-inflammatory M2 phenotype. An excess of the M1 phenotype and a deficiency of the M2 phenotype are crucial to the pathological process of ischemic stroke, but the molecular mechanism is still unclear. Although several studies have confirmed the therapeutic effects of PNS (Panax notoginseng saponins) on ischemic stroke, the precise molecular mechanisms of these effects remain poorly understood. The aim of this study was to investigate the molecular mechanism of PNS influencing microglia polarization via hematopoietic progenitor kinase 1 (HPK1) signaling pathway regulation.

Methods: BV2 cells were pretreated with PNS or GNE-1858 (HPK1 inhibitor) and then polarization into M1- and M2-like phenotypes via lipopolysaccharide + interferon-gamma or interleukin (IL)-4, respectively. Detection of M1- and M2-like phenotypes by flow cytometry. The mRNA levels of tumor necrosis factor-alpha, L-1β, Arg1, and IL-10 were measured by real-time PCR. The phosphorylation levels of HPK1, nuclear factor kappa-B (NF-κB), and c-Jun N-terminal kinase (JNK) were detected by western blot.

Results: The phosphorylation levels of HPK1, NF-κB, and JNK gradually increased under the M1 polarization condition. Under the M2 polarization condition, the phosphorylation levels of HPK1, NF-κB, and JNK gradually decreased. Inhibition of HPK1 activity effectively inhibited the activation of NF-κB and JNK during M1 polarization. PNS can inhibit the activation of JNK and NF-κB by inhibiting the activity of HPK1, thereby inhibiting the polarization of M1-like phenotype and promoting the polarization of M2-like phenotype.

Conclusions: This research confirmed that PNS effectively inhibits M1 microglial polarization while stimulating M2 microglial polarization via HPK1, JNK, and NF-κB signaling pathway suppression.