Alzheimer’s disease (AD) is a severe neurodegenerative disorder that impacts the global impact on the population. Nevertheless, the intricate nature of its pathogenesis has posed significant challenges to drug discovery in this field. This study aimed to verify the therapeutic potential of rubiadin (RB) on AD through both in vivo and in vitro experiments, thereby facilitating translational research for the advancement of AD treatment.
We investigated the neuroprotective effects of RB on AD using both in vivo and in vitro models. Immunohistochemistry and western blot analysis were employed to evaluate inflammatory factors and the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in Mo/HuAPP695swe (APP)/PS1-dE9 (PS1) mice and N2a cells.
RB enhanced the memory performance of APP/PS1 mice in various tests, including the Morris water maze, step-down and step-through passive avoidance tasks, and novel object recognition. RB reduced the accumulation of Amyloid-beta (Aβ) plaques, as shown by immunohistochemical analysis. It also decreased the expression levels of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), while increasing the release of IL-4. Additionally, RB inhibited the NF-κB pathway, as demonstrated by western blot. Moreover, a cell viability test showed that RB protected N2a cells against toxicity caused by Aβ1–42 through a cell viability test. Western blot analysis revealed that neuroinflammation and the NF-κB pathway were inhibited by RB treatment in Aβ1–42-induced N2a cells. Accordingly, RB suppressed the nuclear translocation of NF-κB in Aβ1–42-induced N2a cells.
Our results provide experimental evidence supporting the preclinical research and future clinical applications of RB, thereby facilitating the development of new drugs for AD clinical therapy.
Declining fertility due to ovarian dysfunction is a critical concern for population sustainability. Acupuncture shows potential for ovarian functional restoration, primarily mediated through its neuromodulatory effects on the hypothalamic-pituitary-ovarian (HPO) axis. Accumulating evidence from clinical and animal studies suggests that acupuncture modulates ovarian function through multiple neuroendocrine pathways. Specifically, acupuncture regulates hypothalamic activity by influencing the release of reproduction-associated neuropeptides (e.g., kisspeptin, neuropeptide Y, and gonadotropin-releasing hormone) and neurotransmitters (e.g., gamma-aminobutyric acid, serotonin, glutamate, and dopamine). Additionally, it may affect peripheral-to-central sensory nerve pathways as well as sympathetic and parasympathetic neural activity, which collectively enhance ovarian function. In this article, we comprehensively reviewed the neuroendocrine regulatory pathways through which acupuncture exerts its therapeutic effects in ovarian diseases, thereby providing a deeper understanding of the mechanisms involved and the directions for future research.
Neurodevelopmental disorders [NDDs, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and tic disorder] usually arise during childhood or adolescence, but impact quality of life throughout the whole life cycle. Therefore, early diagnosis of NDDs is necessary; however, its etiology remains unclear. This study aimed to evaluate levels of thyroid, growth, and appetite hormones between children and adolescents with NDDs and healthy controls (HCs) by a meta-analysis of all evidence that demonstrated the importance of these indicators, but yielded controversial results.
Five online databases were searched to retrieve relevant articles published before March 1, 2025. Mean and standard deviation data were collected and pooled using Stata 15.0 software to generate standardized mean difference (SMD) with 95% confidence intervals (CIs) as the effect size (ES) measure.
Fifty-four studies were included. The overall meta-analysis, subgroup, and trim-and-fill adjusting revealed that compared with HCs, levels of thyroid hormone free triiodothyronine (FT3) (SMD = 0.22; 95% CI = 0.04 to 0.40; pES = 0.015), total triiodothyronine (TT3) (SMD = 0.82; 95% CI = 0.36 to 1.28; pES < 0.001), and thyroid peroxidase antibody (TPO-Ab) (SMD = 0.37; 95% CI = 0.08 to 0.67; pES = 0.014) were significantly increased, while free thyroxine (FT4) (SMD = –0.67; 95% CI = –0.69 to –0.64; pES < 0.001), total thyroxine (TT4) (SMD = –0.35; 95% CI = –0.50 to –0.20; pES < 0.001), and thyroid stimulating hormone (TSH) (SMD = –0.22; 95% CI = –0.41 to –0.03; pES = 0.026) were significantly decreased in children and adolescents with NDDs. These changes were mainly observed in ADHD patients, with TPO-Ab increased only in ASD patients. Levels of the appetite hormone leptin were significantly elevated in male NDDs (SMD = 0.74; 95% CI = 0.10 to 1.38; pES = 0.023) and ASD patients (SMD = 0.46; 95% CI = 0.17 to 0.74; pES = 0.002) relative to HCs, but not in ADHD cases. Growth factor IGF-1 (insulin-like growth factor-1) was only significantly lower in the cerebrospinal fluids of ASD patients when compared with HCs (SMD = –0.89; 95% CI = –1.42 to –0.36; pES = 0.001).
Thyroid hormones and IGF-1/leptin may respectively represent promising biomarkers for predicting ADHD and ASD in children and adolescents.
Accurate and timely segmentation of ischemic stroke lesions from diffusion-weighted imaging (DWI) is crucial for diagnosis and treatment planning. Manual segmentation is labor-intensive, time-consuming, and prone to inter-observer variability. This study aims to develop and validate a novel deep learning framework that overcomes the common trade-off between high segmentation accuracy and the computational efficiency required for practical clinical use.
We developed FasterNet and Attention-Gated UNet (FA-UNet), a hybrid U-Net-based architecture. The model’s design features two key innovations: a computationally efficient FasterNet block at the bottleneck to capture global lesion context and multi-scale attention gates (MSAGs) on the skip connections to adaptively refine features and suppress noise. The model was trained and validated on the public Ischemic Stroke Lesion Segmentation (ISLES) 2022 dataset (n = 250 patients) and its performance was assessed on an independent, private test set of 600 DWI scans from 80 patients. FA-UNet’s performance was benchmarked against several state-of-the-art U-Net variants using the Dice coefficient, Intersection over Union (IoU), sensitivity, and precision as primary outcome measures.
On the independent test set (n = 80), the proposed FA-UNet model achieved a Dice coefficient of 0.8676 and an IoU of 0.7584. This performance surpassed all benchmarked architectures, including U-Net, U-Net3plus, and CMU-Net. Compared with the next best performing model, this represents a relative improvement of approximately 1.64% in the Dice score and 1.42% in IoU.
The FA-UNet architecture establishes a new state-of-the-art performance benchmark for automated ischemic stroke segmentation. By effectively balancing high accuracy with computational efficiency, it offers a robust, reliable, and clinically viable tool.
In previous studies, children with developmental dyslexia (DD) have been found to exhibit alterations in auditory sampling within the delta/theta and low-frequency gamma bands in auditory cortical areas during the initial processing stages, which affects the development of phonological skills. It has been suggested that auditory frequency discrimination measures sensory processing in language disorders such as DD. However, it is unclear how the pure-tone frequency discrimination task can detect abnormalities in functional connectivity in DD.
We investigated local and global topological properties of functional networks in electroencephalographic (EEG) frequency bands from δ to γ2 based on a small-world propensity (SWP) model. This was done in both groups during pure-tone frequency discrimination.
Auditory α-, β-, and γ1-networks in the DD group were more integrated and less segregated than those of the control group. They were also not as functionally specialized, as indicated by larger deviations in characteristic path lengths and smaller deviations in clustering. The balanced segregation and integration (moderate clustering and path length) observed in the control group’s γ2-network may explain the optimal structure underlying their better performance. In the low-tone auditory θ- and γ2-frequency networks, the DD group, when compared with controls, lacked hubs in the inferior frontal cortex (IFC) and parietal connectivity to sensory areas. In the control group, however, the superior parietal lobes (SPL) mediated sensory connections. In the high-tone auditory network, only the controls had strong hubs in the right sensorimotor/auditory cortex (δ-frequency), bilateral IFC (γ1), and bilateral anterior temporal cortex (aITG, γ2), while the main hubs in the DD group were only in the left hemisphere. In the γ1 (high-tone) and γ2 (both tones) networks, controls showed strong right frontal-parietal-sensory hubs, which were lacking in the DD group during the task discrimination.
The impairment in low-tone discrimination in the DD group is due to a lack of SPL-prefrontal connectivity within the auditory network. For high-tone discrimination, the DD group showed engagement of only the left-sided auditory network, with bilateral prefrontal recruitment (δ-network). In contrast, the SPL in the control group integrates sensory input for tone prediction, establishing tone-specific sensory/auditory connections with left prefrontal involvement (δ-network). Lower predictability for high tones in the DD group led to more localized processing with prefrontal influence. Overall, reduced frontotemporal connectivity in the DD group may indicate poorer auditory processing. This is likely due to impaired prefrontal-sensory communication and reduced interhemispheric auditory communication, which may underlie perceptual-cognitive biases in tone frequency discrimination.
Ramelteon, a melatonin receptor agonist, has been reported to alleviate postoperative delirium (POD), although its efficacy remains controversial. The mechanisms of ramelteon’s effects are unclear and few animal studies have addressed POD-related behavioral and molecular changes. We investigated the specific postoperative behavioral and molecular changes that result from ramelteon pretreatment.
Ramelteon (0.03 or 0.3 mg/kg, p.o.) was given to mice once a day for 7 consecutive days before abdominal laparotomy under 2 h of isoflurane anesthesia. Postoperative locomotor activity was monitored for 7 days using s.c.-implanted Nano-tag devices in the dorsal region of aged mice (70–80 weeks). One day after surgery, a social interaction test was administered that used a habituation-discrimination paradigm to evaluate social recognition, specifically the ability to distinguish a novel aged intruder from a familiar young intruder after exposure to the latter. Working memory and related cognitive functions were evaluated using the Y maze and novel-object recognition tests. Cytokine levels and microglial activation in the prefrontal cortex and hippocampus were analyzed by western blotting 24 h post-surgery.
Isoflurane anesthesia for 2 h did not impair spontaneous alternation in the Y maze or performance in the novel-object recognition test. However, it induced prolonged hyperactivity and a decrease in social-recognition performance. Pretreatment with ramelteon at a dose of 0.3 mg/kg, but not 0.03 mg/kg, attenuated postoperative hyperactivity and preserved normal social recognition. Furthermore, ramelteon significantly reduced isoflurane-induced elevation of interleukin-1β in the prefrontal cortex but not in the hippocampus.
Isoflurane anesthesia combined with abdominal surgery was associated with prolonged hyperactivity and impaired social recognition, although other cognitive domains such as working memory appeared to remain unaffected. Ramelteon appeared to alleviate these behavioral and neuroinflammatory changes, suggesting its potential for preventing certain postoperative neurobehavioral alterations.
This study aimed to explore the potential relationship between resting-state brain network attributes and adolescent major depressive disorder (MDD), with a focus on understanding how resting-state electroencephalogram (EEG) network features correlate with Hamilton Depression Rating Scale (HAMD) scores, and to identify potential physiological biomarkers for predicting HAMD scores in adolescents with MDD.
Adolescent MDD presents unique neurodevelopmental challenges, yet the neurophysiological correlates of symptom severity remain poorly characterized. This study investigated resting-state EEG network topology and its relationship with HAMD scores in adolescent MDD, aiming to identify potential neural biomarkers for depression severity.
MDD patients exhibited significantly enhanced frontal-parietal connectivity compared with healthy controls (HC) (p < 0.05, false discovery rate (FDR)-corrected). HAMD scores correlated positively with coefficient (Clu) (r = 0.401), global efficiency (Ge) (r = 0.408), and local efficiency (Le) (r = 0.402), while showing a negative correlation with characteristic path length (Cpl) (r = –0.408; all PFDR < 0.05). The regression model achieved strong prediction accuracy (R2 = 0.38, p < 0.001; root mean square error (RMSE) = 2.83), and network features distinguished MDD from HC with 94% classification accuracy.
These preliminary findings deepen our understanding of adolescents with MDD and suggest that resting-state brain network attributes in the alpha band may serve as a potential physiological biomarker for predicting HAMD scores.
Hypoxic/ischemic brain injury remains a major clinical challenge, yet the cellular mechanisms linking oxygen-glucose deprivation/reperfusion (OGD/R) to opioid receptor regulation in human neurons are still not fully understood. The trafficking of μ-opioid receptors (MOR) and κ-opioid receptors (KOR) is a key regulator of neuronal survival under stress. Most studies to date in this field have employed rodent models. However, given the molecular and physiological differences between rodents and humans, this study employed human induced pluripotent stem cell (iPSC)-derived neurons to investigate opioid receptor trafficking during OGD/R, as well as the neuroprotective effects of Herkinorin.
Human iPSC-derived neurons were subjected to 2 h of OGD followed by 24 h of reoxygenation. Cells were treated with Herkinorin (0.1, 0.5, or 1 μM) during OGD/R. Apoptosis was assessed using flow cytometry, while the localization of MOR and KOR in membrane and cytoplasmic fractions was analyzed using western blotting. Western blotting was also used to quantify the expression of apoptosis-related proteins Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved Caspase-3. Statistical comparisons were performed using one-way ANOVA with Tukey’s post hoc test or non-parametric equivalents.
OGD/R significantly increased neuronal apoptosis, upregulated pro-apoptotic Bax and cleaved Caspase-3, and downregulated anti-apoptotic Bcl-2. These changes were accompanied by altered distribution of MOR, but not KOR localization, specifically decreasing cytoplasmic MOR while maintaining membrane levels. Herkinorin, particularly at 1 μM, induced redistribution of MOR from the plasma membrane to cytoplasm, consistent with receptor internalization; it also significantly reduced apoptosis in a concentration-dependent manner. Furthermore, treatment with Herkinorin reversed the OGD/R-induced molecular changes by decreasing the expression of Bax and cleaved Caspase-3, while increasing that of Bcl-2. KOR trafficking remained largely unchanged under all conditions. Importantly, Herkinorin concentrations above 10 μM reduced neuronal viability, indicating a narrow therapeutic window.
Herkinorin exerts neuroprotective effects in human iPSC-derived neurons subjected to OGD/R, potentially by modulating MOR internalization and influencing mitochondrial-dependent apoptotic pathways. However, its efficacy is restricted to a limited dose range (0.1–1 μM), as higher concentrations are toxic. The receptor subtype-specific trafficking pattern observed in this study underscores the importance of human-relevant models for mechanistic and translational research on opioid receptors.
Adding movement sonification to haptic exploration can change the perceptual outcome of a textured surface through multisensory processing. We hypothesized that auditory-evoked emotions influence the appraisal of textured surfaces, with corresponding changes reflected in cortical excitability.
Twelve participants actively rubbed two different textured surfaces (slippery and rough) either without movement sonification, or with pleasant or disagreeable movement sonification.
We found that sounds, whether agreeable or disagreeable, did not change the texture appraisal. However, the less pleasant surface was associated with a stronger negative hedonic valence, particularly when paired with disagreeable movement sonification. Time frequency analyses of electroencephalography (EEG) activities revealed a significant reduction in beta-band power [15–25 Hz] within the source-estimated sensorimotor and superior posterior parietal cortices when contrasting both pleasant and unpleasant sounds with the silent touch. This suggests that the primary somatosensory cortices together with the superior parietal regions participated in the audio-tactile binding, with both pleasant and unpleasant sounds. In addition, we observed a significant increase in beta-band power in medial visual areas, specifically when disagreeable movement sonification was paired with tactile exploration. This may reflect a disengagement of visual cortical processing, potentially amplifying auditory-driven emotional responses and intensifying the perceived unpleasantness of the explored surfaces.
Our results offer new insights into the neural mechanisms by which hedonic valence of auditory signals modulates emotional processing, without disrupting the perceptual analysis of texture properties.
Individuals with atrial fibrillation (AF) are more likely to develop mild cognitive impairment (MCI), but the underlying mechanisms remain unclear. The study aimed to investigate cognitive-related gray matter (GM) volume alterations in stroke-free individuals with AF using voxel-based morphometry (VBM).
3D-T1-weighted magnetic resonance imaging (MRI) scans were obtained from 40 stroke-free AF individuals with MCI (AF-MCI), 40 stroke-free AF individuals with normal cognition (AF-NC), and 40 healthy controls (HCs). GM atrophy was assessed using VBM.
The results revealed widespread GM atrophy in stroke-free individuals with AF, regardless of their cognitive status, with more pronounced GM loss in the AF-MCI group. Significant GM volume reductions were found in several brain regions, including the temporal lobe, parahippocampal gyrus (PHG), cerebellum, and frontal lobe, in the AF-MCI group. Notable reductions in the left PHG and right inferior parietal lobule were observed in the AF-MCI group compared with the AF-NC group. Moreover, decreased GM volume in the left PHG, right superior temporal pole, and right orbital part of the inferior frontal gyrus was positively correlated with cognitive performance.
Among AF individuals free of stroke, degeneration of the PHG correlates with a greater probability of developing MCI. Structural alterations in the brain may be related to the transition from normal cognition to MCI in stroke-free individuals with AF. This study highlights the potential for targeted interventions aimed at slowing cognitive decline in stroke-free AF individuals by focusing on these structural alterations.
Spinal cord injury (SCI) constitutes a profoundly debilitating neurological disorder precipitating motor and sensory function impairment. Curtailing microglia-driven neuroinflammation alongside oxidative stress proves indispensable for efficacious SCI patient management. Poliumoside (POL), a phenylethanoid glycoside molecule, manifests anti-inflammatory, antioxidant, and neuroprotective capacities. Nevertheless, documentation concerning its SCI therapeutic efficacy remains sparse.
Systemic drug toxicity for two POL dosages (15 mg/kg, 30 mg/kg) was evaluated across multiple organs. An SCI murine model was generated employing Allen’s technique. Mice received random assignment into sham, SCI, and SCI+POL cohorts. Intraperitoneal POL administration ensued for 7 consecutive days post-trauma. Histological staining probed tissue and cellular alterations. Functional recuperation was assessed via the Basso Mouse Scale (BMS), hindlimb flexion scoring, and footprint examination. RNA sequencing (RNA-seq) explored POL’s therapeutic impact within SCI. Immunofluorescence detected the axonal marker neurofilament 200 (NF200), myelin marker myelin basic protein (MBP), and the glial scar indicators ionized calcium-binding adapter molecule 1 and glial fibrillary acidic protein (IBA1, GFAP); Western blot (WB) identified the nerve growth-associated protein 43 (GAP43). WB and immunofluorescence quantified inflammatory and oxidative stress markers. POL’s regulatory function within the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) cascade was scrutinized both in vivo and in vitro.
POL intervention induced no systemic organ toxicity. POL-treated mice exhibited pronounced locomotor function enhancement, diminished neuronal tissue depletion, elevated neuronal survival, and attenuated demyelination. RNA-seq analysis illuminated POL’s SCI therapeutic mechanism linkage to axonal regeneration, the phosphatidylinositol signaling apparatus, and the neuronal framework. POL concurrently attenuated glial scar formation and potentiated axonal and myelin regeneration. Mechanistically, POL suppressed pro-inflammatory cytokines and oxidative stress mediators while activating the PI3K/AKT/mTOR pathway.
POL mitigated murine spinal cord injury-induced neuroinflammation and oxidative stress through PI3K/AKT/mTOR signaling pathway activation. Furthermore, POL treatment contracted the glial scar expanse within the injury epicenter and fostered axonal regeneration coupled with myelin regeneration. Consequently, POL enhances post-SCI motor function and accelerates neural function restoration.
The overall pain experience results from the balance between the nociceptive pathway and the body’s endogenous modulation of nociception. The interaction of these systems reduces nociception. Therefore, this study aimed to evaluate how the opioid and dopaminergic systems collaborate to inhibit pain at the peripheral level.
Swiss mice (30–40 g) had their pain sensitivity increased through paw administration of the prostaglandin E2 (2 μg). They then received opioid and dopaminergic receptor antagonists and agonists, along with an inhibitor of endogenous opioid peptide degradation and a dopamine (DA) reuptake inhibitor. The nociceptive threshold was measured using the paw withdrawal test. Groups were compared using one-way analysis of variance (ANOVA), with p < 0.05 considered significant.
The nonselective opioid receptor antagonist naloxone (50 μg/paw) and the selective κ nor-BNI (200 μg/paw; nor-Binaltorphimine) and δ naltrindole (60 μg/paw) receptor antagonists reversed the antinociception caused by peripheral administration of DA (80 ng/paw), but not the μ-opioid receptor antagonist CTOP (20 μg/paw; D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2). The antinociception induced by a submaximal dose of DA (5 ng/paw) was enhanced by bestatin (400 μg/paw), an inhibitor of endogenous opioid peptide degradation. Conversely, peripheral antinociception from submaximal doses of the μ-, δ-, and κ-opioid agonists DAMGO (0.25 μg/paw; [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin), SNC 80 (5 μg/paw; (+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide), and bremazocine (200 ng/paw) was increased by the DA reuptake inhibitor GBR 12783 (16 μg/paw; 1-(2-Diphenylmethoxyethyl)-4-(3-phenyl-2-propenyl)-piperazine). Furthermore, the antinociception from these agonists’ maximum doses was reversed by dopaminergic D2 (remoxipride, 4 μg/paw) and D3 (U99194, 16 μg/paw; 2,3-Dihydro-5,6-dimethoxy-N, N-dipropyl-1H-inden-2-amine) receptor antagonists, but not by the D4 (L-745, 870, 16 μg/paw; 3-(4-[4-Chlorophenyl]piperazin-1-yl)-methyl-1H-pyrrolo[2,3-b]pyridine trihydrochloride) receptor antagonist.
Overall, the data suggest that opioid-mediated antinociception depends on the activation of the dopaminergic system. This demonstrates that pain modulation can be enhanced through the interaction of these systems. Controlling pain at a peripheral level by activating endogenous pathways could be a promising approach to pain management.
Electroacupuncture pretreatment (EA-pre) has been shown to help reduce myocardial ischemia-reperfusion injury (MIRI), but the underlying mechanism remains unclear. Our previous studies indicated that EA activates the cerebellar cortex, specifically the Crus Ⅰ. However, whether activation of the Crus Ⅰ contributes to the attenuation of MIRI induced by EA-pre remains unclear. This study investigated the possible relationship between EA-induced relief of MIRI and the activation of Crus Ⅰ.
Electrocardiogram recording, echocardiography, and cardiac histology staining were used to assess the heart’s functional status. In vivo electrophysiological recordings, Fos-targeted recombination in active populations (Fos-TRAP) gene-labeling technology and chemogenetic viral modulation were used to explore the effects of Crus Ⅰ activation in EA-pre on MIRI.
In vivo electrophysiological recordings demonstrated that Crus Ⅰ plays a crucial role in EA-pre by modulating sympathetic activity to alleviate MIRI. Subsequent Fos-TRAP studies showed that EA stimulation primarily induces changes in the neuronal activity of Crus Ⅰ Purkinje cells (Crus ⅠPC). Chemogenetic viral manipulations further verified that EA-pre suppresses PC activity in MIRI.
EA-pre mitigated cardiac sympathetic nerve dysfunction during MIRI by regulating Crus ⅠPC activity.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with strong genetic and environmental components. Despite progress made over the past decades, no effective therapies targeting the core symptoms of ASD are currently available. More research is required to explore the underlying mechanisms of ASD and discover potential therapeutic targets. Chromodomain helicase DNA-binding protein 8 (CHD8) is one of the most significant high-confidence ASD risk genes identified to date. However, the precise roles and mechanisms of CHD8 in neurodevelopment and behaviors remain incompletely understood. Zebrafish represent an emerging model organism for ASD research. While several zebrafish models with Chd8 disruption have been established, behavioral consequences have not been thoroughly characterized.
Leveraging the high survival rate of homozygous Chd8 mutant males, we comprehensively assessed their behaviors.
The mutants exhibited social deficits across multiple assays, including shoaling, social interaction and three-chamber social preference test. Additionally, anxiety-like behavior, locomotor coordination deficits, and macrocephaly were observed. These phenotypes closely resemble the symptoms in patients carrying disruptive CHD8 mutations.
Our findings establish this Chd8 mutant zebrafish line as a robust model for investigating ASD pathological mechanisms and screening for potential therapies.
In this article, we review clinical, theoretical, and empirical grounds for the consideration of a decisive, yet unrecognized, role of emotions in the psychopathology of acute schizophrenia. We describe accordingly the presence of an emotional syndrome named “Psychotic Arousal” and we further explore its clinical characteristics on the grounds of a psychopathological investigation, including its relevance to recent neurobiological advances. Psychotic arousal has been defined as a diffuse affective state, dominated by abnormal experiences that signify disturbed self-processing, as the brain interacts with external or internal objects. This process may eventually result in the experiential alienation of internal and external reality. Evidence supports that the aberrant experiences are of emotional origin and are seen as abnormal experiential feelings. In addition, this article outlines essential characteristics of the abnormal experiences with arguable biological significance. We propose that they are highly eligible to represent a real pathophysiological process, stemming from a hidden physiology related to the formation of core consciousness and reality perception, with severe consequences for cognition. We underline that the recognition of their medical semiology is important and offers us a unique opportunity to unveil aspects of the physiological mechanism behind the development of delusions and the psychopathology of acute schizophrenia. Moreover, we propose a plausible neurobiological path of investigation based on their phenomenological properties. Finally, we call for the field of Psychopathology to recognize and explore the pivotal role of emotions in the emergence of psychosis and the formation of delusions.
Vascular dementia (VaD) and post-stroke dementia (PSD) are two leading subtypes of vascular cognitive impairment (VCI), each arising from distinct cerebrovascular pathologies. VaD typically results from chronic cerebral hypoperfusion and small vessel disease, leading to progressive executive dysfunction and white matter degradation. In contrast, PSD occurs following acute ischemic events and is frequently associated with hippocampal damage and episodic memory deficits. This review delineates the pathophysiological divergence between VaD and PSD by integrating findings from human clinical studies and preclinical animal models. While rodent models of chronic hypoperfusion replicate key features of VaD, such as oligodendrocyte injury and myelin loss, transient ischemia models—particularly middle cerebral artery occlusion—capture hallmark PSD features, including excitotoxic neuronal death, blood–brain barrier disruption, and glial activation. Emerging research also highlights the involvement of neurovascular unit dysfunction, inflammation-driven neurodegeneration, and region-specific synaptic alterations. Recognizing these mechanistic differences is critical for advancing diagnostic precision, identifying therapeutic windows, and improving translational relevance. Furthermore, the review underscores the need for aged and comorbid animal models, integration of human biomarker studies, and implementation of novel therapies targeting endothelial function, glial reactivity, and cognitive plasticity. Through this comparative approach, we propose a unified framework to guide future investigations and interventions across the spectrum of VCI.