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Pineal region tumors in children are rare and present significant diagnostic and therapeutic challenges due to their deep location, varied histology, and overlapping radiologic features. Mixed germ cell tumors (MGCTs) are particularly rare and may demonstrate complex clinical behavior. We report the case of a 12-year-old boy who presented in August 2024 with progressive headache and nausea. Brain magnetic resonance imaging (MRI) revealed a large pineal mass. Biopsy with endoscopic third ventriculostomy revealed an MGCT composed of 90% immature teratoma and 10% germinoma, with a Ki-67 index of 25%. Serum alpha-fetoprotein (AFP) was mildly elevated (23.2 ng/mL), while beta-human chorionic gonadotropin levels were normal. The patient received six cycles of chemotherapy according to the ACNS1123 protocol for non-germinomatous germ cell tumors. The MRI after chemotherapy showed increased tumor size with cystic/necrotic components and normalization of AFP. Subsequent surgical resection revealed a mature teratoma without malignant elements, consistent with growing teratoma syndrome (GTS). Notably, the Ki-67 index had decreased from 25% at diagnosis to 5% after resection. Given the initial histology and lack of cerebrospinal fluid analysis, adjuvant craniospinal irradiation of 36 Gy with a 54-Gy boost to the tumor bed was delivered according to ACNS0122. The patient tolerated treatment well and remains in good clinical and radiological condition. This case underscores the importance of recognizing GTS and individualizing treatment in pediatric pineal MGCTs.

Traumatic brain injury (TBI) disrupts central nervous system homeostasis, leading to extracellular matrix (ECM) softening and localized hypoxia and thus contributing to astrocytic activation and sustained neuroinflammation. But the interplay between ECM softening and hypoxia in regulating astrocytic activation and response remains elusive. To understand this, we developed an in vitro model incorporating tunable-stiffness hydrogels and a precise oxygen-control system to simulate the mechanical and hypoxic microenvironment of TBI. We characterized the activation-related proteins and cytokine production of astrocytes under the in vitro model, and found that soft ECM and hypoxia independently promote astrocytic activation and synergistically activate astrocytes via HIF-1α/YAP-NF-κB signaling, resulting in astrocytic redox imbalance and neuroinflammation. We further used scanning electrochemical microscopy (SECM) to track the dynamic changes in glutathione (GSH) efflux and membrane integrity in live astrocytes in situ under pathophysiological conditions of ECM softening and hypoxia. The SECM results show that the combined ECM softening and hypoxia progressively impair cellular membrane integrity and promote GSH efflux of astrocytes, corresponding to the early changes in astrocytic function and indicative of an early activation-primed state to exacerbate secondary injury of astrocytes. Last, we found that the lovastatin (a neuroprotective agent) treatment can effectively attenuate astrocytic membrane impairment and decrease GSH efflux, proving the potential of lovastatin to mitigate inflammation and preserve neuroregulatory function. Our work observes the in situ and early state changes of astrocytes under a combined mechanical-hypoxic microenvironment for the first time. The findings offer mechanistic insights into TBI pathogenesis and highlight promising strategies for early therapeutic intervention.

How does the brain build and maintain the precise wiring patterns that distinguish one neuron from another? Clustered protocadherins (PCDHs)-a family of cell-surface molecules that give each neuron a unique identity tag-are central to this process. Their expression is famously controlled by an elaborate locus-specific epigenetic system involving DNA methylation, CTCF binding, and chromatin looping. Whether the activity of the broader epigenetic regulatory machinery is coordinated with protocadherin expression across the human brain has not been systematically tested. Here we show that epigenetic regulators are preferentially co-expressed with protocadherins across multiple human brain regions, suggesting a broader transcriptional coordination than the locus-specific mechanisms previously characterized. Using GTEx v8 RNA-seq data from 2,642 brain samples across 13 regions, we conducted a genome-wide co-expression screen and observed a 6.5-fold enrichment of epigenetic regulators in the top 5% of PCDH-coordinated genes in prefrontal cortex (Fisher's exact p = 2.8 × 10-10). The enrichment replicated independently across additional brain regions, persisted under multiple sensitivity analyses, was preserved after adjustment for cell-type composition, and replicated in an independent brain-bank cohort. The top-ranked epigenetic regulators converge on a defined set of chromatin-remodeling genes implicated in well-characterized neurodevelopmental syndromes. These findings reframe protocadherin biology by extending its epigenetically coordinated context beyond the locus itself to a broader transcriptional program shared with the chromatin-remodeling machinery associated with neurodevelopmental disease. The conceptual advance is consistent with-though does not by itself establish-direct co-regulation, and identifies a specific set of testable mechanistic hypotheses for how disrupted chromatin-remodeling activity in neurodevelopmental disorders may propagate to PCDH-dependent neuronal identity programs in the human brain.

We sought to develop a deep learning (DL) model to enable fully automated 3D segmentation and volumetric assessment of meningioma burden with a specific emphasis on generalizing to high-grade and posttreatment meningiomas to improve interobserver variability and decrease reader time investment in tumor response assessment. In total, 450 postcontrast T1-weighted brain MRIs from 104 patients with meningiomas were obtained from Massachusetts General Hospital and Dana-Farber Cancer Institute. The cohort was unique among prior DL segmentation models in that it encompassed meningiomas of all grades, postoperative, and postradiated meningiomas. Preprocessed MRIs and manually generated tumor segmentations were used to train a U-Net with a joint Dice-cross entropy loss function. When tested on internal data, our model achieved a median Dice of 0.741 and a median 95th percentile Hausdorff Distance (HD95) of 26 mm on a high-grade test set and a median Dice of 0.848 and median HD95 of 1.41 mm on a test set with low-grade tumors. Lesion-wise metrics were equivalent to global metrics for low-grade tumors, which contained only single lesions, but were substantially lower for high-grade tumors, with a median lesion-wise Dice of 0.45 and median lesion-wise HD95 of 130 mm, reflecting greater difficulty delineating individual high-grade lesions. Our model also generalized well to 1000 studies from 944 patients selected from the public BraTS dataset, achieving a median Dice of 0.923 and median HD95 of 2.24 mm. The study produced a model that addresses an unmet need for automated volumetric measurements of meningiomas and created a reliable metric for quantifying meningioma burden. In comparison to prior DL approaches, our model achieved competitive performance on external data and improved Dice scores on high-grade and posttreatment meningiomas. The trained model, volumetric evaluation code, and accompanying documentation are available online at https://github.com/mccle/tumor_segmentation.

Global cerebral ischemia is a well-established experimental model for studying hippocampal vulnerability and memory impairment. This study investigated the neuroprotective potential of Kangen-karyu (KK) in a mouse model of global cerebral ischemia/reperfusion injury induced by bilateral common carotid artery occlusion (BCCAO). Male C57BL/6J mice were subjected to BCCAO followed by reperfusion. KK or nimodipine was administered orally either before or after ischemia. Neurological outcomes, histopathology, and markers of oxidative stress, inflammation, and apoptosis were evaluated. Post-ischemic administration of KK significantly reduced brain edema, neuronal degeneration, and ischemia/reperfusion-induced brain damage, while improving cognitive performance. These effects were associated with decreased phosphorylation of JNK/p38 MAPK and reduced expression of iNOS and apoptosis-related proteins. Post-treatment produced greater benefits than pre-treatment or nimodipine. KK may have therapeutic potential for mitigating global cerebral ischemia/reperfusion-induced brain injury, possibly through modulation of stress- and inflammation-related pathways. Further studies are warranted to validate these findings.

Leptomeningeal metastasis (LM) from gastric cancer is a rare but devastating manifestation of advanced disease. Early diagnosis can be difficult when neurological symptoms are atypical and cerebrospinal fluid (CSF) cytology is negative. We report a 71-year-old man with gastric cardia adenocarcinoma who initially developed hearing impairment, dizziness and gait instability approximately 11 months after radical total gastrectomy, followed by rapidly progressive bilateral hearing loss at presentation. Neurological examination initially showed no meningeal signs or pathological reflexes. Contrast-enhanced brain magnetic resonance imaging (MRI) demonstrated extensive, multifocal linear and patchy leptomeningeal enhancement over the bilateral cerebral hemispheres and cerebellar surfaces. CSF analysis showed marked hypoglycorrhachia, elevated protein, and mild mononuclear pleocytosis, whereas cytology did not identify malignant cells. After alternative infectious and immune-related diagnoses were considered clinically less likely, the findings supported a diagnosis of probable type IIA LM according to the EANO-ESMO criteria. Immunohistochemistry of the primary gastric tumor showed CK7 positivity, diffuse CAM5.2 positivity, partial CDX-2 nuclear positivity, HER2 immunohistochemistry (IHC) 2+ membranous staining, mutant-pattern p53 expression, and a Ki-67 proliferation index of approximately 90%. The disease progressed rapidly to impaired consciousness, and the family chose best supportive care after a multidisciplinary team (MDT) discussion. This case highlights that leptomeningeal metastasis from gastric cancer may initially present with hearing impairment; integrated assessment of MRI findings, CSF biochemistry, clinical course, and careful consideration of alternative diagnoses is essential.

There is a growing need for alternative animal models to evaluate central nervous system (CNS)-targeted therapies, and pigs are emerging as a promising option. Their translational utility depends on accurate estimates of CNS tissue and cerebrospinal fluid (CSF) volumes, which are important for the design and interpretation of preclinical dosing studies. A cross-sectional magnetic resonance imaging (MRI) study was conducted in 12 domestic Yorkshire-Landrace pigs (Sus scrofa) across four postnatal age groups (2, 5, 11, and 19 weeks). MRI was performed on the brain and spinal cord using T2-weighted turbo spin echo with fat saturation and short tau inversion recovery sequences. CNS tissue and CSF volumes were segmented and quantified for brain and spinal compartments, along with linear measurements of brain cavity dimensions, spinal cord and canal lengths, and regional spinal cord and subarachnoid space dimensions. Age-associated differences were observed across groups, including increases in CNS tissue and CSF volumes, CNS length, and multiple brain and spinal anatomical measurements. Notably, spinal CSF volume exceeded brain CSF volume in older pigs, indicating a shift in CSF compartmental distribution that may be relevant to dosing and delivery considerations for CNS-targeted therapies. This study provides MRI-derived, age-specific estimates of brain and spinal CSF and CNS tissue volumes in juvenile pigs, which may inform anatomical assumptions and study design considerations for CNS-focused preclinical research.

Individuals with Alzheimer's disease dementia show Alzheimer's disease pathology and a heterogeneous degeneration of the Substantia Nigra (SN) post-mortem. However, it is unclear how SN degeneration is related to cognitive dysfunction across the Alzheimer's disease dementia continuum. In this study, using data from the prospective DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE), we investigated whether in vivo SN MRI measures are lower in individuals with clinically defined Alzheimer's disease dementia than in healthy control subjects (HC) and if they are associated with hippocampal functional activity during the processing of novel visual stimuli and subsequent recognition memory. One hundred and sixty DELCODE participants (69&#x2005;years &#xb1; 6&#x2005;years, 88 men), including 79 HC, 70 individuals with subjective cognitive decline (SCD), 17 individuals with mild cognitive impairment (MCI) and 10 individuals with Alzheimer's disease dementia, completed a scene novelty and encoding task and a 3T SN-sensitive MRI scan, from which the two in vivo SN measures MRI contrast and volume were calculated and harmonized between scanner sites while preserving diagnostic group differences. For 71 individuals, CSF levels of phosphoTau, total tau and amyloid-beta 42/40 ratio (A&#xdf;42/40) were available. All individuals completed a neuropsychological task battery from which a global cognitive score was calculated. In separate models, we assessed the relationship between SN MRI markers and CSF levels of Alzheimer's disease, the global cognitive score, hippocampal novelty activation and recognition memory while accounting for age, sex, years of education and total intracranial volume (TIV). SN volume but not SN MRI contrast was lower in individuals with clinical Alzheimer's disease dementia [one-way analyses of covariance (ANCOVA); F(156,4) = 5.6665, P = 0.0010, n = 160]. SN MRI contrast and volume were not associated with A&#xdf;42/40, ptau and total tau CSF levels (all P > 0.1) or hippocampal novelty activation (all P > 0.1). Moreover, SN volume was positively associated with recognition memory (R 2 = 0.07, P < 0.001, n = 159), global cognition (R 2= 0.38, P < 0.0001, n = 160) and years of education (R 2 = 0.03, P = 0.036, n = 160). Our study emphasizes the potential of using in vivo SN MRI markers to study the impact of SN degeneration on general cognitive impairment and recognition memory in an Alzheimer's disease dementia cohort. Our results motivate future longitudinal studies to explore how SN volume and SN contrast change with disease progression, how these are differentially associated with cognitive decline, and how SN volume and SN contrast might be related to other dopamine-dependent cognitive functions and dysfunctions.

While osteoarthritis (OA) has long been viewed primarily as a localized, mechanically-driven joint disorder, emerging evidence suggests that systemic factors may play a significant modulating role in its pathogenesis. This review presents the "Gut-Brain-Liver-Kidney axis" as a potential regulatory framework to explore a conceptual shift towards a systemic perspective on this traditionally localized disease. Available evidence is synthesized to clarify how gut microbiota dysbiosis and its metabolites contribute to systemic inflammation and disrupt joint homeostasis through specific pathways, such as the GUDCA-FXR-GLP-1 axis. Bacterial extracellular vesicles are further highlighted as essential nanoscale messengers facilitating communication between the gut and joints. Extending beyond gut health, the significant impact of central sensitization and neuroendocrine dysregulation in the brain is investigated as a key driver of chronic pain perception-a phenomenon often disproportionate to observable structural damage. Unlike mechanisms that directly cause cartilage breakdown, central sensitization primarily modulates pain experience and can secondarily influence disease progression by promoting maladaptive behaviors (e.g., reduced mobility). The liver's involvement is also analyzed, particularly its disorders related to iron and lipid metabolism that promote chondrocyte ferroptosis. Furthermore, the analysis addresses how renal dysfunction intensifies OA by impairing vitamin D metabolism and leading to the accumulation of uremic toxins, such as indoxyl sulfate. By integrating these interconnected systemic pathways, a complex network of potential novel therapeutic targets is revealed. Consequently, innovative strategies aimed at these axes are outlined, including the use of probiotics, vagus nerve stimulation, FGF21, GalNAc-siRNA, and vitamin D supplementation. This perspective encourages moving beyond symptom management toward mechanism-based, multi-targeted strategies. Key unanswered questions are outlined and priorities for future research and clinical translation in this evolving field are proposed.

Increased racial and ethnic diversity in population neuroscience research is widely understood to facilitate better identification of subgroup effects and more generalizable findings. Consistency in reporting race and ethnicity population descriptor variables would allow the research community to better assess progress toward more representative datasets. One important lever for ensuring robust and consistent reporting of population descriptors are journal guidelines, and this review of current guidelines finds that there are opportunities for neuroscience journals to strengthen scientific rigor by more clearly delineating expectations with respect to reporting and operationalizing race and ethnicity population descriptors.

Traumatic Brain Injury is prevalent during military service and is associated with short- and long-term psychosocial and functional changes, though comprehensive longitudinal data on Veterans and active-duty service members (SMs) are lacking. To address this research gap, we utilized data from the Long-term Impact of Military-relevant Brain Injury Consortium (LIMBIC) and the Translational Research Center for TBI and Stress Disorders (TRACTS), two prospective longitudinal cohort studies of veterans and active duty SMs, each containing a wide range of symptom scales, objective assessments, and health-related outcomes. This paper describes the innovative methods used to achieve the initial proof-of-concept harmonization for baseline psychosocial and physical health data from these two large cohort studies. To achieve harmonization, we gathered a multidisciplinary team with clinical and research expertise. We created a list of measures utilized by each study and organized them into larger clinically meaningful domains. When possible, we harmonized full measures, or single items directly, while others needed to be indirectly harmonized, by recoding, aligning categorical levels, and categorizing scales based on established cut scores. We calculated descriptive statistics to summarize and compare data. We then conducted Principal Component Analysis (PCA) for all continuous measures to assess whether site-level effects were observed in the shared variance. A total of 73 variables capturing psychosocial function, sensorimotor, pain, and clinical health factors were harmonized across the LIMBIC and TRACTS studies. There were no differences in sex or ethnicity distributions between the studies. Sensory, social health, and health related clinical data were broadly comparable across cohorts, while pain intensity and headache disability were higher in LIMBIC. PCA analysis suggests data is suitable for pooled analysis. We were able to directly harmonize multiple self-report measures of social well-being and indirectly harmonize other functional and demographic variables. While this initial effort focused on baseline data, the included principles can be employed to harmonize longitudinal data to increase the ability to detect clinical phenotypes to be applied in precision medicine approaches in future research.

Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis. This study is aimed at establishing an ubiquitin-proteasome system (UPS)-related prognostic model and investigating its link to immune infiltration and therapy response. GBM datasets were obtained from public databases. Ubiquitin-proteasome system-related genes (UPSGs) were identified from literature. Consensus clustering defined UPS-based GBM subtypes. Differentially expressed genes (DEGs) were screened, and a prognostic model was constructed using univariate Cox, least absolute shrinkage and selection operator (LASSO), and stepwise regression. The model's performance was validated using survival analysis and time-dependent receiver operating characteristic (ROC) curves. Immune infiltration was assessed using single-sample gene set enrichment analysis (ssGSEA), TIMER, and ESTIMATE. Drug sensitivity was assessed by correlating the half-maximal inhibitory concentration (IC50) of candidate drugs with the risk score. Single-cell RNA sequencing data were used to characterize UPSG expression across distinct cell subpopulations in GBM. For in vitro validation, key UPSGs were silenced in GBM cell lines, and cell proliferation, migration, and invasion were measured using Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays, respectively. Two UPS-related GBM subtypes were identified. Six genes (IGFBP6, CTSD, SPAG4, ZNF560, COL22A1, and HOXC13) formed the prognostic model, where high Riskscore indicated poor survival. High Riskscore correlated with greater immune infiltration, including CD8+ T cells and macrophages. IC50 values of 24 drugs were significantly associated with Riskscore. Single-cell analysis revealed seven GBM subpopulations; notably, COL22A1 was enriched in MES-like cells, and CTSD in macrophages. IGFBP6 promoted GBM cell proliferation, migration, and invasion. This study establishes a UPS-based prognostic model for GBM that links immune infiltration and drug sensitivity, providing potential biomarkers and therapeutic targets for GBM.

Migraine is characterized by high prevalence, recurrent attacks, and poor response to pharmacological interventions, which can severely impair patients' quality of life. The complex and diverse aura symptoms in its clinical presentation further increase the risk of misdiagnosis and mismanagement. Moreover, the pathogenesis of this disorder remains incompletely understood. This study employed a visual stimulation paradigm combined with blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) to simultaneously monitor brain functional activity and neuronal dynamics in patients with visual aura migraine (VaM) and migraine without aura (MwoA). The aim was to identify specific brain network features associated with visual aura in VaM, thereby providing new insights into its pathological mechanisms and early differential diagnosis. From May 2023 to May 2024, 21 patients meeting the diagnostic criteria for VaM and excluding related ocular fundus and optic nerve pathologies during the interictal period (VaM group), 21 patients meeting the criteria for MwoA during the interictal period (MwoA group), and 21 gender- and age-matched healthy controls (HC group) were recruited from the Department of Neurology, Affiliated Hospital of North Sichuan Medical College. All participants underwent visual stimulation using an 8&#x202f;Hz flickering checkerboard paradigm concurrent with task-state fMRI scanning and image acquisition. The primary outcome was the comparison of brain activation differences among the three groups and between each pair of groups using one-way analysis of variance (ANOVA) and post-hoc multiple comparison analyses. Secondary outcomes included within-group brain activation analysis for the VaM, MwoA, and HC groups using one-sample t-tests. Brain regions showing differential activation among the VaM, MwoA, and HC groups included: right cerebellar lobule IX, left middle temporal gyrus, left orbital part of the inferior frontal gyrus, left triangular part of the inferior frontal gyrus, left opercular part of the inferior frontal gyrus, left temporal pole: superior temporal gyrus, left medial superior frontal gyrus, left anterior cingulate gyrus, left middle cingulate gyrus, right middle cingulate gyrus, right middle occipital gyrus, left middle occipital gyrus, left superior occipital gyrus, left middle temporal gyrus, right angular gyrus, left precuneus, right precuneus, and left cuneus (p&#x202f;<&#x202f;0.05). Pairwise comparisons revealed: Compared to the HC group, the VaM group exhibited stronger activation in the left precuneus (p&#x202f;<&#x202f;0.005). Compared to the HC group, the MwoA group showed stronger activation in the right middle occipital gyrus (p&#x202f;<&#x202f;0.005) and left middle occipital gyrus (p&#x202f;<&#x202f;0.05). Compared to the MwoA group, the VaM group demonstrated stronger activation in the right angular gyrus (p&#x202f;<&#x202f;0.05), left cuneus (p&#x202f;<&#x202f;0.0001), right middle cingulate gyrus (p&#x202f;<&#x202f;0.05), and left precuneus (p&#x202f;<&#x202f;0.05). Conversely, the VaM group showed weaker activation than the MwoA group in the right middle occipital gyrus (p&#x202f;< 0.05). The results indicate abnormalities in visual-related brain networks in both patient groups, suggesting a central mechanism underlying visual aura generation in VaM. Abnormal activation in regions such as the cuneus, precuneus, and superior occipital gyrus may serve as preliminary indicators that warrant further investigation into visual aura mechanisms, while changes in the middle cingulate gyrus and angular gyrus may be associated with cognitive-emotional aspects of migraine, although this remains exploratory.

Alzheimer's disease (AD), the most common cause of dementia in older adults, is characterized by progressive cognitive decline, synaptic dysfunction, and neuronal loss. Among the multifactorial mechanisms implicated in AD, reciprocal interactions between brain-derived neurotrophic factor (BDNF) and amyloid-&#x3b2; (A&#x3b2;) have attracted increasing attention as a convergent axis linking amyloid pathology to impaired neurotrophic support. BDNF promotes neuronal resilience, synaptic plasticity, and cognitive function primarily through the activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and downstream signaling pathways, including PI3K-Akt and MAPK/ERK. Human postmortem and biomarker studies mainly support associations between reduced BDNF signaling, synaptic dysfunction, and AD-related pathology. In contrast, cell-based and animal studies provide mechanistic evidence that BDNF/TrkB signaling may influence amyloid precursor protein (APP) processing and neuronal resistance to A&#x3b2;-induced stress. Conversely, mechanistic studies indicate that A&#x3b2; accumulation can suppress CREB-dependent BDNF expression, disturb BDNF transport, and impair TrkB receptor function. Thus, the BDNF-A&#x3b2; relationship is better interpreted as a stage- and context-dependent pathogenic coupling rather than a simple causal loop. This review synthesizes evidence from human studies, animal models, and cellular systems to clarify how BDNF-A&#x3b2; dysregulation contributes to AD progression and to discuss the translational potential of BDNF-oriented interventions.

Spectrin Repeat-Containing Nuclear Envelope Protein 1 (SYNE1) is important gene for maintaining neuronal structure and function, particularly in the cerebellum, the brain region responsible for coordinating movement. The genetic mutation in SYNE1 gene, which encodes Nesprin-1 protein leads to autosomal recessive form of spinocerebellar Ataxia OMIM (608441). This cerebellar dysfunction causes progressive balance and coordination problems, including reflexes and cognitive impairment. To understand genetic mutations in SYNE1 gene that are linked with Autosomal Recessive Spinocerebellar Ataxia type 8 (SCAR8) and Autosomal Recessive Cerebellar Ataxia type 1 (ARCA1). The study was done in the Center of Excellence in Genomic Medicine and Research (CEGMR) during 2023-2024. Firstly, Whole Exome Sequencing (WES) was carried out to identify the mutation, followed by Sanger sequencing to validate the WES results. WES identified a novel homozygous stop-gained variant, NM_182961.3:c.352C>T (p.Arg118Ter), in the SYNE1 gene in a 32-year-old Saudi patient. This alteration was associated with progressive cerebellar atrophy, impaired fine motor skills, muscular weakness, and speech and learning deficits. The variant was independently confirmed by Sanger sequencing. The patient's phenotype was consistent with previously reported ARCA1 and SCAR8. To our knowledge and based on the currently available literature, this may represent the first reported Saudi family with a SYNE1 mutation associated with these conditions. This finding advances the genetic and molecular characterization of these rare disorders, highlights the utility of molecular diagnostics, and supports the establishment of a local database of disease-associated variants to improve diagnosis, management, and future research in the Saudi population.

We investigated the interaction of the brain-derived neurotrophic factor (BDNF) gene variant, Val66Met, with the effect of prenatal/neonatal environmental conditions on anxiety-like behavior in adulthood in rats. In a genetic Val66Met rat model, we compared the effects of a high-enrichment/high-complexity early-life environment (HE) and a low-enrichment/low-complexity environment (LE). Body weight was higher in both male and female HE rats compared to LE rats. Anxiety-like behavior on a plus maze or in an open field was enhanced in both male and female HE rats compared to LE rats. In contrast, following HE, only in females, adrenal weight was higher, and in the forced swim test, immobility was lower, and swimming was higher. Body weight and behavioral changes did not differ between BDNF genotypes. Fear conditioning and extinction were not affected. The effect of HE vs. LE condition on expression of BDNF, the antioxidant transcription factor, NRF2, and the glucocorticoid receptor, NR3C1, in the ventral hippocampus varied depending on genotype, and most of these changes were again only seen in females. There were no effects on the expression of the stress markers, SGK1 and FKBP5, or the mineralocorticoid receptor, NR3C2. These results show persistent effects of early-life environment on anxiety-like behavior and gene expression of BDNF and stress markers in adulthood, with some effects showing sex- and Val66Met genotype specificity. These results may be important for our understanding of factors involved in the development of clinical anxiety and depression, and also have implications for animal welfare in the laboratory setting.

Donation after circulatory death (DCD) liver transplantation is currently limited by inferior outcomes compared with donation after brain death (DBD), predominantly due to ischaemia-reperfusion injury and biliary complications. Abdominal normothermic regional perfusion (aNRP) is an emerging graft-preservation technique that aims to improve graft viability, patient outcomes and reduce rate of complications in DCD liver transplantation. The aim of this review is to appraise the current literature on the utility of aNRP in liver transplantation surgery. The PRISMA guidelines for systematic reviews were followed and relevant databases searched. Primary outcomes were graft and patient survival rates. Secondary outcomes were primary non-function, early allograft dysfunction, biliary complications including ischaemic cholangiopathy (IC)/ischaemic type biliary lesions (ITBL) and retransplantation rates. Risk-of-bias analysis was conducted. Narrative synthesis was performed due to marked heterogeneity in the included studies. Fourteen studies (2014-2026) encompassing 1,278 transplanted aNRP liver grafts were included in this review. aNRP was associated with a reduction in IC/ITBL rates, lower rates of primary non-function and lower early allograft dysfunction compared with conventional retrieval (super rapid recovery followed by static cold storage). Graft loss and retransplantation rates were also lower in aNRP cohorts. Compared with DBD transplantation, aNRP outcomes were similar with near-zero rates of IC in both groups. No significant differences were also observed between aNRP and ex situ normothermic machine perfusion (NMP). aNRP is associated with reductions in biliary complications, graft loss and retransplantation compared with conventional DCD retrieval, with outcomes comparable to DBD and ex situ NMP and offers a solution to expand the donor pool.

Epileptic seizures are serious neurological events that significantly affect patients' health and quality of life. Accurate seizure prediction is essential for enabling early intervention and improving clinical outcomes. Most existing prediction systems are patient-specific, requiring large amounts of individualized data and exhibiting poor generalizability across subjects. A major challenge in this field lies in the limited availability of preictal EEG segments, recorded shortly before a seizure onset, compared to the more abundant interictal segments, which represent normal brain activity between seizures. This study proposes a hybrid deep learning architecture for patient-independent epileptic seizure identification. The framework is designed to perform robustly across multiple patients without the need for subject-specific calibration. A data augmentation technique based on a random walk algorithm was adopted from the literature to address the scarcity of preictal EEG segments. Then the power spectral density (PSD) was used to extract features, capturing important frequency-domain characteristics of brain activity. The proposed hybrid architecture integrates a Hierarchical Temporal Separable Convolutional Network (HTSCN), a Dual-Stage Bidirectional Recurrent Neural Network (DS-Bi-RNN), and a Multi-Head Attention Mechanism, enabling effective extraction of spatial, temporal, and contextual features from non-stationary EEG signals while addressing inter-patient variability. Experimental evaluations conducted on the CHB-MIT and Siena datasets demonstrated the strong discriminative performance of the proposed model in classifying preictal and interictal EEG states, achieving test accuracies of 98.74% and 97.35%, respectively. These results highlight the robustness and generalization capability of the architecture, establishing it as a promising approach for scalable and clinically applicable epileptic seizure prediction systems, though further validation on continuous EEG streams is warranted to fully characterize alarm rates in real-world deployment.

This study aimed to characterize the prenatal imaging features of brain and cardiac lesions associated with tuberous sclerosis complex (TSC), with particular focus on fetal magnetic resonance imaging (MRI) findings, and to explore the complementary role of fetal MRI, fetal echocardiography, and genetic testing in prenatal evaluation. This retrospective study analyzed prenatal neurocardiac MRI findings in fetuses diagnosed with TSC or cardiac rhabdomyomas through genetic and/or clinical assessment between 2018 and 2025. Twenty-four fetuses with TSC were included, 23 underwent fetal brain MRI, which revealed abnormalities in 15 cases, including subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytoma. Subependymal nodules appear as hypointense on T2-weighted imaging (T2WI) (14/14, 100%), and the vast majority appear as hyperintense on T1-weighted imaging (T1WI) (12/14, 85.7%), while most show hyperintensity on diffusion-weighted imaging (DWI) (11/14, 78.6%). Cortical dysplasia included cortical tubers and white matter migrational abnormalities. Cortical dysplasia shows hyperintensity on T1WI in all cases (8/8, 100%), hypointensity on T2WI (6/8, 75%), and predominantly hyperintensity on DWI (6/8, 75%). Subependymal giant cell astrocytoma appears hypointense on T2WI and hyperintense on T1WI. According to our research, T1WI was superior to T2WI in demonstrating cortical dysplasia. Intracranial lesions in tuberous sclerosis complex manifest as hyperintense on T1WI (contrasting with the dark background of white matter), a phenomenon often referred to as the "bright spot" sign. Cardiac MRI was performed in 12 of the 24 fetuses. Cardiac rhabdomyomas appear as hyperintense signals on T2WI against the dark background of the myocardium (12/12, 100%), a finding commonly referred to as the "bright spot" sign. The "bright spot" sign on MRI has significant diagnostic value for fetal TSC, particularly for identifying cortical dysplasia and cardiac rhabdomyoma. In cases of suspected TSC or cardiac rhabdomyoma, combining prenatal ultrasound with MRI enhances diagnostic accuracy, facilitating better clinical management.