Hyperuricemia (HUA) is a prevalent metabolic disorder closely linked to neuropsychiatric symptoms, including emotional disturbances. However, the neural mechanisms underlying this association remain largely unexplored. We established a mouse model of acute HUA by administering potassium oxonate (PO) and hypoxanthine (HX) intraperitoneally to investigate its effects on emotional behaviors and neural activity in the medial prefrontal cortex (mPFC). The HUA mice exhibited typical hyperuricemia and renal morphological abnormalities, along with increased anxiety-like behaviors, but showed no alterations in mechanical/thermal pain sensitivity or depressive-like behaviors. Immunofluorescence c-Fos mapping revealed extensive activation in emotion-related brain regions, such as the mPFC, paraventricular thalamus (PVT), anterior insular cortex (aIC), lateral hypothalamus (LH), and basolateral amygdala (BLA). Whole-cell patch-clamp recordings demonstrated that HUA was associated with reduced intrinsic excitability of mPFC layer V/VI pyramidal neurons, indicated by a lower firing rate, higher rheobase, and decreased membrane input resistance. Additionally, it was associated with alterations in the excitatory/inhibitory (E/I) synaptic balance, including changes the frequency of spontaneous excitatory postsynaptic currents (sEPSCs). Notably, the reduction in mPFC neuronal excitability was comparable between sexes, although female HUA mice displayed less pronounced synaptic alterations in response to HUA. S-equol, a selective estrogen receptor beta ligand, ameliorated anxiety-like behaviors associated with HUA. Electrophysiological analyses revealed that S-equol appeared to restore the intrinsic excitability of mPFC pyramidal neurons in both sexes, although it did not significantly alter E/I synaptic balance. However, its behavioral effects exhibited sex-dependent differences: S-equol significantly ameliorated anxiety-like behaviors in both sexes, with the specific behavioral domains affected varying between males and females. The results suggest that HUA may be linked to anxiety-like behaviors, potentially involving reduced excitability of mPFC pyramidal neurons. Furthermore, S-equol may exert anxiolytic effects in association with restored neuronal excitability, independently of detectable changes in E/I synaptic balance. Together, this study offers new insights into the neurobiological mechanisms underlying HUA-related emotional disorders and identifies sex-specific potential therapeutic targets.

Major depressive disorder (MDD) is a common psychiatric disorder, and accumulating evidence suggests that astrocytes play an important role in the regulation of emotional behaviors. However, the mechanisms by which astrocytes in the hypothalamic paraventricular nucleus (PVN) contribute to chronic stress-induced depression remain unclear. In this study, a chronic restraint stress (CRS) mouse model was established, and depressive-like behaviors were assessed using the sucrose preference test, open field test, tail suspension test, and forced swim test. Immunofluorescence staining, chemogenetic manipulation, fiber photometry, transcriptomic analysis, and quantitative real-time PCR were employed to investigate the role of PVN astrocytes and their interactions with excitatory neurons. CRS induced robust depressive-like behaviors and was accompanied by reactive astrocyte activation in the PVN, as evidenced by increased GFAP expression and morphological remodeling. Fiber photometry recordings revealed enhanced astrocytic calcium activity under both basal and stress-related behavioral conditions following CRS exposure. Chemogenetic activation of PVN astrocytes induced depressive-like behaviors in naïve mice, whereas inhibition of astrocytic activity alleviated depressive-like behaviors in CRS mice. Moreover, CRS increased c-Fos expression and calcium activity in CaMKIIα-positive excitatory neurons within the PVN. Bidirectional modulation of astrocyte activity correspondingly altered excitatory neuronal activity, indicating a functional coupling between these cell populations. Transcriptomic screening combined with qPCR validation further identified upregulated expression of the stress-responsive genes Timp4 and Manf in the PVN following CRS. Collectively, these findings demonstrate that PVN astrocytes are critical regulators of chronic stress-induced depressive-like behaviors and suggest that the PVN astrocyte-excitatory neuron functional axis represents a potential therapeutic target for depression.

Recanalization is central to acute ischemic stroke treatment. However, reopening an occluded artery does not always restore microvascular perfusion, and hemorrhagic transformation (HT) can occur regardless of recanalization success. Neutrophil extracellular traps (NETs) may help explain these discordant outcomes because they act within occlusive thrombi, the downstream microcirculation, and the neurovascular interface. This review examines the roles of NETs in thrombolysis resistance, no-reflow, and hemorrhagic injury. Within thrombi, NET-associated chromatin reinforces clot architecture and limits fibrinolysis. Intravascular NETs may impede downstream microvascular flow after recanalization, while NET-related inflammatory signaling may aggravate blood-brain barrier disruption and HT. These findings implicate NETs in impaired recanalization, incomplete tissue reperfusion, and hemorrhagic injury and support their evaluation as an adjunctive target during reperfusion therapy.

Neurostimulation has emerged as a potential approach for modulating autonomic and neuroimmune function. Because epipharyngeal mucosa receives sensory innervation from cranial afferents, mechanical stimulation of this region may engage neural pathways. Epipharyngeal abrasive therapy (EAT) involves mechanical and chemical stimulation of the epipharyngeal mucosa and is used clinically for chronic epipharyngitis; however, its central and systemic effects remain poorly understood. This study aimed to investigate whether epipharyngeal stimulation using EAT is associated with changes in brainstem functional connectivity and circulating proteomic profiles in healthy adults. Participants underwent five EAT sessions at 7-day intervals (Protocol A), with restingstate functional MRI performed before, immediately after, and four weeks after the first session. A subset also underwent a control protocol without EAT (Protocol B). Wholebrainstem seed-to-voxel functional connectivity was analyzed. Paired plasma samples collected before and after the first EAT session were analyzed using the SomaScan 11 K assay. Longitudinal analysis identified altered connectivity between the brainstem and subcallosal/medial frontal region, primarily immediately after EAT. A controlled withinsubject analysis identified an EAT-specific increase in connectivity between the brainstem and right temporal pole, extending into the inferior temporal gyrus. Proteomic analysis identified 13 proteins meeting exploratory screening criteria and significant pathway-level enrichment involving RNA metabolism, translation, and extracellular matrix organization. Mechanical and chemical stimulation of the epipharynx was associated with changes in brainstem-cortical functional connectivity and circulating proteomic signatures. These findings suggest that sensory stimulation of the epipharynx may engage cranial sensory afferent-brainstem pathways and contribute to coordinated central neural and peripheral molecular responses.

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), is difficult to prevent due to limited understanding of the mechanisms underlying the transition from acute to chronic pain and the lack of objective neuroimaging biomarkers for individualized risk stratification. In this study, we aimed to develop interpretable machine learning models based on hippocampal subfield radiomics to classify zoster-associated pain (ZAP) patients and identify neuroimaging biomarkers reflecting microstructural alterations in hippocampus associated with ZAP. High-resolution 3D T1-weighted MR images were obtained from 28 PHN patients, 25 Hz patients, and 21 healthy controls (HCs). We extracted radiomic features of ten hippocampal subfields and used five machine learning classification algorithms to identify the most contributive subfield and robust model for classifying ZAP patients. Furthermore, SHapley Additive exPlanations (SHAP) was used to interpret the optimal model. In distinguishing ZAP patients from HCs, the SVM_Linear model based on the left subiculum radiomics achieved the highest performance with an AUC of 0.739, whereas the Logistic_L1 model based on the right CA4-DG and left SR-SL-SM radiomics showed the best performance with an AUC of 0.799 in distinguishing PHN patients from HZ patients. SHAP analysis revealed that SmallAreaEmphasis from the right CA4-DG subfield was the dominant feature for identifying PHN patients, followed by ClusterShade from the left SR-SL-SM subfield. Furthermore, both features showed strong associations with disease duration. These results suggest that hippocampal subfield radiomics can effectively stratify ZAP phases. Specifically, right CA4-DG radiomic features may serve as effective neuroimaging biomarkers associated with disease chronicity and have the potential for early risk stratification and intervention of ZAP.

Apelin-13, a bioactive peptide that acts via the APJ receptor, exhibits potent anti-oxidant, anti-apoptotic, and anti-inflammatory properties. However, its role in intracerebral hemorrhage (ICH) remains poorly understood. In this study, we aimed to investigate the therapeutic potential of Apelin-13 and the underlying mechanisms in a mouse model of ICH.

Spinal cord injury (SCI) often leads to severe motor and sensory dysfunction, yet no effective treatment currently exists. Epidural spinal cord stimulation (ESCS) is a treatment for chronic neuropathic pain in the trunk and extremities, and exerts a significant effect on the recovery of motor function, although the underlying mechanisms remain unclear. The present study aimed to investigate the effects of ESCS on the endogenous neural stem cells (eNSCs) proliferation and neuroprotection as well as the underlying mechanisms following SCI in rats. In the present study, results showed that ESCS improved hindlimb motor function and markedly increased the numbers of surviving ventral horn neurons of the spinal cord at 7 and 28 days after SCI. ESCS significantly reduced the apoptosis of anterior horn cells in the spinal cord on day 28 post-SCI. Moreover, ESCS remarkably increased the expressions of NSCs markers nestin and sox2, as well as the proportion of nestin/sox2/DAPI-double positive cells (eNSCs) at 7 days after SCI. Notably, ESCS induced only a negligible number of Sox2/NeuN/DAPI double-positive cells at 28 days after SCI. LY294002, a selective inhibitor of phosphoinositide 3-kinase (PI3K) markedly decreased the ratios of eNSCs and surviving ventral horn neurons after ESCS treatment. Finally, ESCS increased the protein levels of phosphorylated-protein kinase B (p-Akt) and phosphorylated-mammalian target of rapamycin (p-mTOR) at 7 days after SCI, and LY294002 significantly attenuated the effects of ESCS on p-Akt and p-mTOR. This report suggests that ESCS treatment after SCI enhances the expansion of eNSCs and neuroprotection via the PI3K/AKT/mTOR signaling pathway.

Lower respiratory tract infections (LRTIs) represent one of the most frequent causes of sepsis. Sepsis-associated encephalopathy (SAE), a serious complication of sepsis, markedly increases patient mortality and the risk of long-term cognitive impairment. The emerging concept of the lung-brain axis offers a novel framework for understanding the pathogenesis of SAE. Unlike general reviews covering all-cause sepsis-associated encephalopathy, this review specifically focuses on SAE secondary to LRTI, and discriminates its unique epidemiological, clinical and mechanistic signatures from SAE triggered by abdominal, urinary or bloodstream infection. This review systematically summarizes the epidemiological characteristics of SAE induced by LRTIs, the anatomical and immunological basis of lung-brain interactions, and key pathological mechanisms including neuroinflammation, blood-brain barrier (BBB) disruption, neurotransmitter imbalance, and mitochondrial dysfunction. Additionally, it highlights advances in biomarker research and clinical management strategies. By integrating evidence from molecular‑biology and neuroimaging studies, this article describes how pulmonary infections drive brain dysfunction via neural, immune, and endocrine pathways. These findings provide a theoretical foundation to support early diagnosis and targeted therapeutic interventions.

This study examined age-related differences in behavior and brain dynamics underlying cognitive-motor interference (CMI) during motor dual-tasks (DT) with increasing motor task complexity. Behavioral performance and electrocortical activity were assessed in 19 younger adults (11 males, 8 females; 25.5 ± 2.3 years) and 11 older adults (6 males, 5 females; 72.6 ± 4.6 years) using mobile electroencephalography (EEG). Participants performed an oddball choice-reaction task under three conditions: sitting, standing, and treadmill walking. Event-related potential (ERPs; P1, N1, P3) amplitudes and latencies, response times, postural sway, and gait parameters were recorded to evaluate CMI. Data were analyzed using repeated-measures ANOVAs with within-subject factors of motor condition and stimulus type and age group as a between-subject factor. Older adults exhibited reduced step length compared to younger adults, but no DT-related changes in gait or postural sway were observed. Response times were generally slower in older adults and increased from sitting to standing and walking whereas younger adults showed slowing only from sitting to standing. Early sensory ERP components (P1, N1) demonstrated increased amplitudes with higher motor demands. The P3 component was reduced in amplitude in both groups during walking, with delayed latencies in older adults. For both groups, P3 latencies were associated with prolonged response times. Our findings suggest that this slowing during walking reflects altered cognitive resource allocation, characterized by delayed central information processing and enhanced early visual processing, rather than impaired peripheral motor coordination.