Neuroreport最新文献

Objective: Neonatal hypoxic-ischemic brain damage (HIBD) can cause short- and long-term neurological damage. MicroRNA (miR)-204-5p is closely associated with nerve injury caused by brain injury, but its mechanism in HIBD is not very clear.

Methods: The neonatal rat's HIBD model was constructed by the modified Rice-Vannucci method, and the expression of miR-204-5p was detected. After overexpression or knockdown of miR-204-5p and application of Wnt2 activator HLY78, the histopathological changes and neuronal degeneration in the hippocampal CA1 region were observed with pathological staining. The neurological function was assessed with a diving platform test and elevated plus-maze test. Nerve regeneration-related protein and Wnt2/Ephrin-A2 (Eph receptor-interacting proteins)/EphA7 (erythropoi-etin-producing hepatomocellular receptor) signaling pathway protein levels were detected by immunohistochemistry and western blot, respectively.

Results: miR-204-5p was highly expressed in HIBD. When miR-204-5p was knocked down, the morphology of nerve cells and Nissl bodies was notably improved, Fluoro-Jade C and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells number was significantly reduced. The levels of brain-derived neurotrophic factor and growth-associated protein 43 were significantly increased, and the behavioral indicators of the diving platform and elevated plus-maze test were significantly alleviated. The nerve injury was repaired, and the Wnt2/Ephrin-A2/EphA7 signaling pathway protein was notably elevated. The overexpressed miR-204-5p aggravated the nerve injury in HIBD rats. After the application of HLY78, the neuropathological damage of HIBD rats was further repaired, and the nerve regeneration and function were also significantly improved.

Conclusion: Knockdown of miR-204-5p can improve HIBD in neonatal rats by activating the Wnt2/Ephrin-A2/EphA7 signaling pathway to encourage nerve regeneration and functional recovery.

Objective: This study aimed to elucidate the neuroprotective mechanisms of paeonol in ameliorating chronic stress-induced amygdala neuronal injury via modulation of the glycogen synthase kinase-3β (GSK3β)/calcineurin signaling pathway. Paeonol, a polyphenolic compound from Moutan Cortex , exhibits therapeutic effects. Studies show it alleviates lipopolysaccharide-induced depression-like behaviors in mice, though its mechanisms remain unclear.

Methods: Forty-eight Sprague-Dawley rats were divided into four groups: control, chronic unpredictable mild stress (CUMS) model, low-dose paeonol (25 mg/kg), and high-dose paeonol (80 mg/kg). Paeonol was administered intragastrically 1-week post-CUMS induction for 4 weeks. Behavioral tests assessed depression-like behaviors. Neuronal morphology was evaluated via hematoxylin and eosin, Nissl, and Golgi staining, while western blot quantified cofilin1, p-cofilin1, GSK3β, and calcineurin expression.

Results: CUMS rats exhibited depressive-like behaviors, neuronal nuclear pyknosis, interstitial edema, hyperchromatic cytoplasm, and reduced Nissl body integrity. Golgi staining revealed increased dendritic complexity and spine density. CUMS upregulated p-cofilin1 and GSK3β while downregulating total cofilin1 and calcineurin. Paeonol treatment alleviated depressive behaviors, reduced neuronal damage, and normalized dendritic complexity and spine density. Molecularly, paeonol suppressed p-cofilin1 and GSK3β expression while restoring cofilin1 and calcineurin levels.

Conclusion: Chronic stress induces dendritic hypertrophy and spine hyperplasticity, contributing to depressive phenotypes. Paeonol counteracts these effects, likely by modulating the GSK3β/calcineurin pathway, highlighting its therapeutic potential for stress-related neuronal injury.

Objective: Traumatic brain injury (TBI) results in severe long-term sequelae. While mesenchymal stem cell-derived exosomes (MSC-Exos) have demonstrated the ability to regulate microglial responses and neuroinflammation, their impact on neutrophil inactivation, particularly in relation to neutrophil extracellular traps (NETs), has not yet been fully elucidated. This research was designed to explore the potential involvement of MSC-Exos in modulating NET formation and microglial polarization following TBI.

Methods: A murine TBI model and an in-vitro lipopolysaccharide-induced microglial activation model were utilized to evaluate the effects of miR-26a-5p-enriched exosomes on NET inhibition, microglial polarization, reduction of neuroinflammation, and promotion of neural function recovery.

Results: Treatment with MSC-Exos post-TBI reduced NET formation and decreased microglial polarization into a proinflammatory phenotype. Genome-wide prediction detected miR-26a-5p as a predominant component of MSC-Exos, which was closely associated with TAB2. Functional assays demonstrated that miR-26a-5p suppressed NET formation in neutrophils and modulated microglial polarization. MRI and histopathological assessments confirmed that MSC-Exos enriched with miR-26a-5p significantly reduced neuronal death and lesion volume. Moreover, miR-26a-5p was found to regulate microglial polarization and reduce neuroinflammation via the TAB2/JNK/AP1 signaling pathway. Cognitive assessments employing the Morris Water Maze and Modified Neurological Severity Scores revealed significant improvements in neural function following treatment.

Conclusion: These findings underscore the potential of MSC-Exos-miR-26a-5p to inhibit NET formation, modulate microglial polarization toward an anti-inflammatory phenotype, and enhance recovery from neural damage in TBI through the TAB2/JNK/AP1 pathway.

Objective: Cerebral infarction (stroke) is a major global public health issue. This study explores the mechanisms by which electroacupuncture affects motor function after cerebral infarction by combining complementary experimental approaches in middle cerebral artery occlusion mice. The work focuses particularly on the Wnt/hypoxia-inducible factor-1 alpha (HIF1A)/netrin-1 signaling axis and downstream targets, including netrin-1 and vascular endothelial growth factor (VEGF), to provide a comprehensive understanding of the mechanisms that underpin electroacupuncture stimulation after stroke.

Methods: The middle cerebral artery occlusion model was established with electroacupuncture intervention. The cerebral cortex of mice was collected for detections, including RNA sequencing, western blot, immunofluorescence, quantitative PCR, and so forth. HIF1A-overexpressing and knockdown cell lines in SH-SY5Y cells were used for further verification.

Results: Exosome and RNA sequencing identified the key microRNA mir-210 and the Wnt/HIF1A/netrin-1 signaling axis after electroacupuncture treatment at head acupoints in the murine model. In addition, the HIF1A transcription factor was upregulated and bound to promoters of genes for netrin-1 and VEGF thereby activating transcription of these loci. Dual luciferase reporter assays revealed that mir-210 targets the gene for the tumor suppressor adenomatous polyposis coli, thereby stimulating the Wnt-signaling pathway. Furthermore, behavioral experiments demonstrated that electroacupuncture intervention in the Wnt/HIF1A/netrin-1 signaling axis improved motor function in middle cerebral artery occlusion mice.

Conclusion: The study reveals that electroacupuncture stimulation promotes angiogenesis and neural reconstruction after cerebral infarction by regulating the Wnt/HIF1A/netrin-1 signaling axis through mir-210, and suggests novel therapeutic targets for the treatment of cerebral infarction with electroacupuncture.

Background: Rhegmatogenous retinal detachment (RRD) is known to induce functional alterations in the gray matter regions associated with vision. However, the impact of RRD on the white matter (WM) connectome remains largely unexplored.

Methods: We applied graph theory to evaluate the functional network topology of the WM connectome in RRD patients. A support vector machine (SVM) classifier, combined with SHapley Additive exPlanations (SHAP), was then employed to distinguish RRD patients from healthy controls (HCs) and to identify key brain regions driving model predictions.

Results: Compared to HCs, RRD patients exhibited significant disruptions in both global and nodal network topology. Network-based statistics identified 23 subnetworks with altered connectivity. Notably, the integration of SVM and SHAP analyses revealed that betweenness centrality (Bc) was the most discriminative topological feature, achieving an area under the curve of 0.9211.

Conclusion: These findings suggest that RRD disrupts critical hubs within the central visual and higher-order cognitive networks, leading to characteristic network reorganization. Moreover, Bc shows promise as an early neuroimaging biomarker for RRD. Overall, our results advance the understanding of neuroadaptive changes in RRD and support the clinical application of network topological metrics in early diagnosis.

Background: The incidence of postoperative cognitive dysfunction (POCD) in elderly patients is high and related to an increased postoperative mortality rate. Magnolol has the potential to improve cognitive function, but its therapeutic effects and mechanisms of action on POCD remain unclear.

Methods: An aged mouse model of POCD was constructed using sevoflurane anesthesia and abdominal exploratory surgery. Magnolol was administered via intragastric gavage at doses of 10 or 20 mg/kg daily, starting 1 week before surgery. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown mice were used to investigate the role of the Nrf2/antioxidant response element (ARE) pathway in the therapeutic effects of magnolol on POCD.

Results: In POCD mice, magnolol treatment significantly reduced the escape latency, increased crossing numbers in the platform quadrant and target quadrant dwell time, and enhanced the novel object recognition index. Meanwhile, under the action of magnolol, the morphology of hippocampal neurons was protected, the rate of cell apoptosis was reduced, and the expression of antiapoptotic protein B-cell lymphoma 2 was upregulated. Magnolol also reduced the levels of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-1β, and reactive oxygen species, while increasing the levels of superoxide dismutase, glutathione, and glutathione peroxidase. In addition, magnolol activated proteins related to the Nrf2/ARE pathway. Notably, silencing Nrf2 weakened the effect of magnolol on improving cognitive function in POCD mice.

Conclusion: Magnolol may effectively improve POCD in aged mice by activating the Nrf2/ARE pathway.

Background: Previous studies have shown that two core subregions of the prefrontal cortex - the dorsolateral prefrontal cortex (DLPFC) and the inferior frontal gyrus (IFG) - are both closely related to cognitive control in creativity; however, the similarities and differences in their cognitive control mechanisms during creativity remain to be further clarified.

Methods: This study employed a within-subject design, using transcranial direct current stimulation to manipulate the activity of left DLPFC and IFG separately. Participants completed divergent and convergent thinking tasks under three conditions: anodal stimulation of the left DLPFC, cathodal stimulation of the left IFG, and sham stimulation. The novelty and appropriateness of generated answers during idea generation, as well as those selected during idea selection, were compared across conditions.

Results: (a) Anodal stimulation of the left DLPFC significantly enhanced the novelty of answers generated during idea generation in both the alternate uses task (AUT) and the product improvement task and helped to select the more appropriate answer during idea selection in AUT. (b) Cathodal stimulation of the left IFG significantly improved the novelty of ideas generated in the AUT but had no significant effect on performance during idea selection.

Conclusion: The cognitive control mechanisms of the left DLPFC and IFG differ during the creative process. Anodal stimulation of the left DLPFC enhances goal-directed cognitive control, thereby promoting creativity, whereas cathodal stimulation of the left IFG facilitates the generation of creative ideas by releasing inhibitory control over semantic retrieval.

Objective: This study aimed to investigate the role of alectinib in a neonatal mouse model of germinal matrix hemorrhage (GMH).

Methods: We induced GMH in postpartum day 5 mouse pups by injecting collagenase into the germinal matrix. Alectinib was administered intraperitoneally after GMH induction. Western blot, immunofluorescence staining, and quantitative PCR were performed to explore the effects of alectinib on oxidative stress, microglial number, proinflammatory cytokines expression, blood-brain barrier (BBB) damage, and cortical neuron loss. Cresyl violet and Prussian blue staining were used to detect the ventricular size, cerebral cortical atrophy, and hemorrhage burden. Novel object recognition and rotarod tests were used to determine the neurological function.

Results: We found that anaplastic lymphoma kinase (ALK) was upregulated in the perihematomal areas following GMH and was presented in endothelial cells. Treatment with alectinib resulted in a reduction in oxidative stress, as shown by decreasing generation of reactive oxygen species, lipid peroxidation, and oxidative DNA at 3 days after GMH. Alectinib also attenuated the number of microglia, levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α, loss of BBB integrity ZO-1 and claudin-5, and disruption of BBB. These effects of alectinib were accompanied by reduced hemorrhage burden, cortical neuron loss and cerebral cortical atrophy, and improved motor coordination, cognitive and memory impairments at 23 days after GMH.

Conclusion: Our data revealed that alectinib reduced oxidative stress, microglia number, and BBB permeability, thereby alleviating secondary brain injury in GMH. Therapies that inhibit ALK signaling may confer neuroprotection against GHM.

Objective: Menthol is widely used as a cooling agent and an adjunctive analgesic to relieve various painful conditions, such as migraine. As menthol acts as an agonist for the thermosensitive ion channel transient receptor potential melastatin 8 (TRPM8), other ion channels, such as voltage-gated Na + channels, are also involved in the antinociceptive effect of menthol. In this study, we explored the effect of menthol on tetrodotoxin-resistant (TTX-R) Na + channels in nociceptive sensory neurons.

Methods: TTX-R Na + current (I Na ) was recorded from acutely isolated rat dural afferent neurons identified with the fluorescent dye DiI using a whole-cell patch-clamp technique.

Results: Under a voltage-clamp condition, menthol potently decreased the amplitude of the persistent TTX-R Na + current (I Na ) in a concentration-dependent manner, with a minor effect on the transient current. The inhibition of persistent TTX-R I Na by menthol was not affected by the TRPM8 antagonist. Menthol (300 μM) (1) shifted the steady-state fast inactivation relationship to hyperpolarizing ranges without affecting the voltage-activation relationship, (2) accelerated the onset of inactivation, and (3) retarded the recovery from the inactivation of TTX-R Na + channels. Under the current clamp condition, menthol (300 μM) decreased the threshold for action potential generation but reduced the number of action potentials elicited by strong depolarizing current stimuli.

Conclusion: The results of this study suggest that menthol exerts an analgesic effect by preferentially inhibiting persistent TTX-R I Na and modulating the inactivation and recovery kinetics of TTX-R Na + channels.

Background: Although previous neuroimaging studies have revealed alterations in the static brain networks of patients with high myopia, little is known about changes in their dynamic brain networks, particularly regarding directional connectivity within these networks, warranting further investigation.

Methods: In this study, resting-state functional MRI was conducted on 82 confirmed patients with high myopia and 59 healthy controls. Employing dynamic Granger causality analysis, sliding time windows, and K-means clustering, we assessed dynamic alterations in effective connectivity within the brain's functional networks in patients with high myopia.

Results: Patients with high myopia show significantly enhanced dynamic effective connectivity (dEC) between the visual network and the default mode network (DMN) compared with healthy controls. Furthermore, aberrant connectivity is detected between the visual network and the limbic network. In addition, intravisual network dEC is markedly increased. In state 1, the frequency differed significantly between the two groups, with high myopia patients showing a markedly higher frequency than healthy controls.

Conclusion: This study found that patients with high myopia exhibit significantly altered patterns of dEC, especially increased connectivity between the visual network, the DMN, and the limbic network. Furthermore, significantly increased intranetwork dEC within the visual network indicates enhanced internal visual information processing. These findings offer new insights into the neural mechanisms of high myopia and suggest that long-term visual impairment may trigger functional reorganization in both visual and nonvisual brain networks.