Neuroscience最新文献

{"title":"A zebrafish model unravels the role of PHF21A in neurodevelopment and epilepsy","authors":"Ting Wang ,&nbsp;Xueyang Niu ,&nbsp;Shijia Ouyang ,&nbsp;Miaomiao Cheng ,&nbsp;Haipo Yang ,&nbsp;Changhao Liu ,&nbsp;Fan Mei ,&nbsp;Yuehua Zhang","doi":"10.1016/j.neuroscience.2025.08.007","DOIUrl":"10.1016/j.neuroscience.2025.08.007","url":null,"abstract":"<div><h3>Background</h3><div>The <em>PHF21A</em> gene encodes the protein BRAF histone deacetylase complex 80 (BHC80), which is primarily expressed in the human brain and essential for neurodevelopment and seizures. However, the implications of <em>PHF21A</em> variants in human disease pathogenesis have yet to be fully elucidated.</div></div><div><h3>Methods</h3><div>Whole-exon sequencing was performed on three patients with <em>PHF21A</em> variants. The associated phenotype was validated using a <em>phf21ab</em>-knockout zebrafish model generated via CRISPR/Cas9 technology.</div></div><div><h3>Results</h3><div>Three patients exhibited de novo <em>PHF21A</em> pathogenic variants associated with infantile epileptic spasm syndrome (IESS). Notably, developmental delay was evident in all cases prior to seizure onset. One patient presented with comorbid autism spectrum disorder (ASD) and macrocephaly. Brain MRI of two patients showed widening of the frontotemporal subarachnoid space and ventriculomegaly. Following therapeutic intervention, two patients achieved seizure remission. To further elucidate the functional consequences of <em>PHF21A</em> deficiency, we conducted comprehensive morphological, behavioral, and electrophysiological analyses in <em>phf21ab</em>-knockout zebrafish model. Compared with the cas9 control group, compared with the Cas9 control group, the <em>phf21ab</em> knockout group exhibited significant reductions in the area of the forebrain, midbrain, and whole brain. Electrophysiological assessments revealed epileptiform discharges in 6 of 25 <em>phf21ab</em>-knockout zebrafish.</div></div><div><h3>Conclusion</h3><div>These findings collectively suggest that <em>PHF21A</em> pathogenic variants exert substantial impacts on neurodevelopment and seizure disorders. The observed neuroanatomical alterations and epileptogenic activity in the zebrafish model reveal an important role of <em>PHF21A</em> in neurodevelopment and epilepsy.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"584 ","pages":"Pages 138-147"},"PeriodicalIF":2.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liver X receptor agonists in central nervous system disorders: From neuroprotection to clinical challenges","authors":"Qian Zhang ,&nbsp;Jin-Dong Mao ,&nbsp;Min Wang ,&nbsp;Hui Chen ,&nbsp;Qin-Fei Wang ,&nbsp;Kun Zhang ,&nbsp;Le Yang ,&nbsp;Xue Ma ,&nbsp;Chuan Wang ,&nbsp;Yu-Mei Wu","doi":"10.1016/j.neuroscience.2025.07.050","DOIUrl":"10.1016/j.neuroscience.2025.07.050","url":null,"abstract":"<div><div>Central nervous system (CNS) disorders, which include both neurodegenerative and neuroinflammatory conditions, present significant therapeutic challenges due to their complex pathological mechanisms, limited treatment options, and difficulties in drug delivery across the blood–brain barrier (BBB). Therefore, exploring therapeutic targets capable of overcoming these obstacles is of paramount importance. The liver X receptor (LXR) plays a crucial role in lipid homeostasis, inhibition of neuroinflammation, and promotion of neurogenesis, making it a promising therapeutic target for CNS diseases. However, the potential adverse effects associated with LXR agonists, such as hepatic steatosis and hypertriglyceridemia, may hinder their future clinical application. In this review, we examine the dual roles of LXR agonists in CNS diseases, highlighting their therapeutic benefits alongside their adverse effects. To address these challenges, we propose several optimization strategies, including the development of LXRβ selective agonists, advanced nano-delivery systems, and combination therapies, with the ultimate goal of providing a theoretical foundation for future therapies centered on LXR.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"584 ","pages":"Pages 148-159"},"PeriodicalIF":2.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized controlled trial of theta burst stimulation modalities in severe post-stroke aphasia: examining the right hemisphere’s role","authors":"Yanhong Dai ,&nbsp;Hong Wang ,&nbsp;Qun Fang ,&nbsp;Jiajian Yan ,&nbsp;Leyi Xu ,&nbsp;Zhaowen Zhou ,&nbsp;Liwei Mao ,&nbsp;Zhuoming Chen","doi":"10.1016/j.neuroscience.2025.08.003","DOIUrl":"10.1016/j.neuroscience.2025.08.003","url":null,"abstract":"<div><div>This randomized controlled trial explores the therapeutic potential of theta burst stimulation, a form of transcranial magnetic stimulation, in treating severe post-stroke non-fluent aphasia, with a focus on the role of the right hemisphere. While traditional TMS protocols often target the left hemisphere or suppress the right hemisphere, emerging evidence suggests variability in treatment efficacy. Theta burst stimulation, a distinctive protocol within transcranial magnetic stimulation modalities. We compared intermittent theta burst stimulation (an excitatory protocol) and continuous theta burst stimulation (an inhibitory protocol) applied to the triangular region of the right inferior frontal gyrus against sham stimulation. All participants received daily personalized speech training alongside stimulation. Language function and quality of life were assessed using the Western Aphasia Battery and Stroke and Aphasia Quality of Life Scale, respectively. Results indicated that all groups showed improvements in language function and quality of life, but the intermittent theta burst stimulation group exhibited significantly greater gains in spontaneous speech, repetition, naming, and overall aphasia severity compared to both continuous theta burst stimulation and sham groups. No significant differences were observed between continuous theta burst stimulation and sham groups. These findings suggest that excitatory stimulation of the right inferior frontal gyrus may enhance language recovery in severe non-fluent aphasia, potentially through compensatory mechanisms of the right hemisphere. This study contributes to refining neuromodulation strategies for post-stroke aphasia rehabilitation.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"585 ","pages":"Pages 198-205"},"PeriodicalIF":2.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and targeted treatments of cobalt-encephalopathy from cobalt-chromium orthopedic implants","authors":"Tong Wu,&nbsp;Haoran Li,&nbsp;Wu-Ya Chen","doi":"10.1016/j.neuroscience.2025.08.008","DOIUrl":"10.1016/j.neuroscience.2025.08.008","url":null,"abstract":"<div><div>5–10 million persons are living with cobalt-chromium joint or spinal implants therefore are systemically exposed to ionic and nanoparticulate cobalt-chromium metallosis degradation products from wear or corrosive mechanisms. Cobalt’s toxidrome (cobaltism) is characterized by neurologic, cardiovascular, immune, and constitutional symptoms and findings. Orthopedic-Implant-Cobaltism (OIC) became recognized in 2010 related to metal-on-metal hip resurfacings and replacement of which two million were fitted before largely silent market recall. Recently the at-risk population has be expanded to any person with a cobalt-chromium orthopedic component of a hip, shoulder, knee, or spinal reconstruction.</div><div>The Cobaltism- Symptom-Inventory (CSI) is a validated clinical screening tool for Orthopedic-Implant-Cobaltism. The CSI score increases when urinary cobalt exceeds 1 ppb or urine-cobalt-years exposed exceeds 10 ppb-years. This review explores the pathophysiology of cobalt encephalopathy focusing on cellular hypoxia, antioxidant imbalance, and mitochondrial damage. It also examines the role of microglia and oligodendrocytes in neurodegenerative diseases following cobalt exposure, m6A methylation modification, and proline isomerase Pin1 function. It further discusses current research on potential options for the treatment of cobalt toxicity, including glucagon-like peptide-1 and gastric inhibitory polypeptide, D-β-hydroxybutyrate, and inhibitors of NF-κB and p38 MAPK.</div><div>Implant removal is currently the most effective method to reduce blood cobalt levels and halt the progression of OIC. However, revision joint and spinal operations are highly morbid and expensive though likely mandated in extreme cases. It is important to develop medical treatments that reduce systemic cobalt exposure from indwelling cobalt-chromium orthopedic implants and mitigate or reverse the cobalt related neurodegeneration.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"584 ","pages":"Pages 32-47"},"PeriodicalIF":2.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-specific recurrent insulin-induced hypoglycemia (RIIH) effects on ventromedial hypothalamic nucleus astrocyte metabolic sensor expression and glycogen metabolism","authors":"Sushma Katakam,&nbsp;Subash Sapkota,&nbsp;Madhu Babu Pasula,&nbsp;Rami Shrestha,&nbsp;Rajesh Yadav,&nbsp;Karen P. Briski","doi":"10.1016/j.neuroscience.2025.07.042","DOIUrl":"10.1016/j.neuroscience.2025.07.042","url":null,"abstract":"<div><div>Brain astrocytes support neuron energy stability by maintaining an energy reserve and by catabolizing glucose to the transferrable oxidizable fuel L-lactate. Astrocyte-neuron metabolic coupling shapes ventromedial hypothalamic nucleus (VMN) counterregulatory neurotransmission. VMN astrocyte involvement in recurring insulin-induced hypoglycemia (RIIH)-associated sex-specific acclimation of these neurochemical signals is unclear. Current research implemented combinatory <em>in situ</em> immunocytochemistry/laser-catapult-microdissection/Western blotting and micropunch-dissection/HPLC-electrospray ionization-mass spectrometry methods to investigate whether RIIH alters VMN astrocyte glucose sensing and glycogen metabolism according to sex. Data disclose distinctive effects of single and repetitive hypoglycemia exposure on glucose transporter-2, glucokinase, and total/phosphorylated 5′-AMP-activated protein kinase protein profiles in dorsomedial (dm) versus ventrolateral (vl) VMN astrocytes. Acute hypoglycemia down-regulated VMNdm and VMNvl astrocyte glycogen synthase protein; in each sex, this inhibitory response was abolished (VMNdm) or persisted (VMNvl) during RIIH. Singular hypoglycemia respectively up- or down-regulated glycogen phosphorylase-brain (GPbb) and −muscle type (GPmm) proteins in female VMN astrocytes, responses that were correspondingly amplified by or refractory to RIIH. Male astrocytes exhibited RIIH-associated habituation of VMNdm GPbb (inhibitory) and GPmm (stimulatory) responses to hypoglycemia. Acute hypoglycemia amplified (male) or decreased (female) glycogen levels in each VMN division. RIIH exacerbated (VMNdm) or normalized (VMNvl) glycogen augmentation in males, yet reversed glycogen diminution in the female VMNdm, not VMNvl. Results show that RIIH elicits VMN division-specific adjustments in male and female astrocyte glucose and energy sensing functions and tissue glycogen content. Further research is needed to examine whether precedent hypoglycemia-associated acclimation of VMNdm and/or VMNvl astrocyte glucose handling controls sex-specific counterregulatory neurotransmission and hormone secretion during RIIH.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"584 ","pages":"Pages 93-106"},"PeriodicalIF":2.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional role of the perirhinal cortex in encoding and retrieval of Pavlovian trace fear conditioning","authors":"Yen-Ling Huang ,&nbsp;Yu-Rui Liu ,&nbsp;Chun-hui Chang","doi":"10.1016/j.neuroscience.2025.07.048","DOIUrl":"10.1016/j.neuroscience.2025.07.048","url":null,"abstract":"<div><div>The perirhinal cortex (PRC) and the thalamic reuniens (Re)/rhomboid (Rh) nuclei (ReRh) participate in the regulation of trace fear learning, likely through their respective reciprocal interconnections with the medial prefrontal cortex (mPFC) and the hippocampus (HPC). We previously demonstrated that ReRh inactivation impaired the acquisition, but not the retrieval, of trace fear memory. Moreover, the retrieval of trace fear memory acquired under ReRh inactivation only reprised when the ReRh was brought off-line. To explore the role of the PRC in trace fear regulation, we pharmacologically inactivated the PRC before trace fear acquisition and/or retrieval in this study. Our results showed that PRC inactivation during either phase resulted in a decrease in fear response during the early test session compared to controls. We also noticed that without the proper function of the PRC during both the acquisition and retrieval, the rats displayed a high level of fear during the early test session but declined rapidly toward the latter trials compared to controls. The results suggested that although the retrieval of trace fear memory acquired under PRC inactivation recurred during PRC inactivation, the fear memory was relatively fragile. Finally, for rats with or without functional PRC, disruption of NMDA-dependent plasticity in the dorsal HPC (DH) during conditioning resulted in defects of trace fear learning in both scenarios. Collectively, our results indicated that functional PRC is involved in the regulation of trace fear acquisition and retrieval, and that trace fear acquisition is hippocampus-dependent regardless of the PRC being on-line or off-line.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"583 ","pages":"Pages 93-102"},"PeriodicalIF":2.8,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144779405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential therapeutic targets for hypoxic-ischemic brain injury based on mitochondrial reprogramming mechanism","authors":"Li-Min Yang,&nbsp;Hong Cui,&nbsp;Li-Jun Yang","doi":"10.1016/j.neuroscience.2025.07.043","DOIUrl":"10.1016/j.neuroscience.2025.07.043","url":null,"abstract":"<div><div>Hypoxic-ischemic brain injury (HIBI) is a prevalent global health challenge, which is characterized by high disability and mortality rates. Despite extensive research, effective therapeutic interventions that can mitigate the influences of this disease and reduce associated disability and mortality rates remain elusive. Hypoxia-ischemia-induced energy deficiency in brain tissue not only impairs neurons but also disrupts the structural and functional integrity of mitochondria. This review focuses on mitochondrial reprogramming in hypoxia-ischemia brain injury and targeting mitochondrial reprogramming as a therapeutic goal to mitigate mitochondrial damage and restore neuronal energy supply. Mitochondrial reprogramming refers to a series of adaptive changes (including changes in size, fusion, fission, transport and anchoring) that mitochondria undergo in response to changes in cellular metabolism under physiological or pathological conditions. Our systematic summary of new therapeutic directions for mitochondrial reprogramming in hypoxic-ischemic brain injury models, particularly the mechanism of action of MitoQ, Ferrostatin-1analogue (UAMC-3203), to protect damaged neurons, points to a new therapeutic strategy for neonatal hypoxic-ischemic brain injury disorders.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"583 ","pages":"Pages 76-83"},"PeriodicalIF":2.8,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144763922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the stress system of the grieving brain: corticotropin-releasing factor receptors and partner loss in coyotes (Canis latrans).","authors":"Rachel Tong, Sara M Freeman","doi":"10.1016/j.neuroscience.2025.07.049","DOIUrl":"10.1016/j.neuroscience.2025.07.049","url":null,"abstract":"<p><p>Forming social bonds is fundamental in helping us foster connections with others. The loss of a loved one often results in grief, stress, and loneliness, and the stress response system of the body has been implicated in the physiological symptoms associated with grieving. Corticotropin releasing factor (CRF) is the hormone that initiates the stress response in the body and acts at two different receptor subtypes CRF receptor (CRFR)1 and CRFR2. Many studies on CRF and social loss have been conducted in monogamous prairie voles, but studies in longer-lived monogamous mammals could improve understanding of the effects of losing pair bonds. A monogamous mating system and stable pair bonding behavior exhibited by coyotes (Canis latrans) make them an appropriate animal model to study social bonds and social loss. Our goal of this larger study was to map CRFR1 and CRFR2 in the coyote brain using a competitive binding approach and to quantify CRFR levels in both widowed and paired female coyotes, allowing us to determine if CRFRs densities changed in response to partner loss. The results of our mapping study showed that the olfactory system, hippocampus, and amygdala were sites of action of CRFRs. Region-specific differences in CRFR1 and CRFR2 binding were observed after partner loss. Specifically, elevated CRFR1 and CRFR2 binding were detected in widows in the olfactory bulb and olfactory tubercle respectively, suggesting a potential role of the olfactory system in regulating the brain's response to social loss in coyotes.</p>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of novel disease-causing variants and their influence on clinical presentation in dihydrofolate reductase deficiency","authors":"Dandan Wang,&nbsp;Dengyu Zhou,&nbsp;Yuanyuan Zhang,&nbsp;Weiwei Lu,&nbsp;Zhihua Luo","doi":"10.1016/j.neuroscience.2025.07.045","DOIUrl":"10.1016/j.neuroscience.2025.07.045","url":null,"abstract":"<div><div>Dihydrofolate reductase (DHFR) deficiency is a rare autosomal recessive disorder of folate metabolism, which is crucial for DNA/RNA synthesis and normal growth. Only seven molecularly confirmed cases, all presenting with megaloblastic anemia and neurological symptoms, have been reported. We report two cases from a non-consanguineous Chinese family. The proband presented with neonatal seizures; folic acid improved neurological symptoms but did not prevent fatal respiratory failure. His sister had severe megaloblastic anemia. Whole-exome sequencing identified two compound heterozygous variants in <em>DHFR</em> (p.Gly18Val and p.Pro26Leu) in both patients. Structural modeling suggested these variants to compromise protein stability/function. Variant protein expression plasmids produced significantly less DHFR protein than wild-type plasmid as indicated by western blot and ELISA analyses. Methotrexate fluorescence binding assays indicated reduced binding capacity, suggesting potential structural alterations in the variant proteins. These results demonstrate that the variants lead to decreased DHFR protein abundance and perhaps altered molecular interactions, supporting their pathogenicity. Our findings underscore the critical importance of early genetic testing for patients with megaloblastic anemia or neurological symptoms to diagnose <em>DHFR</em> deficiency. Early detection and treatment are essential to improve prognosis and prevent severe outcomes.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"583 ","pages":"Pages 84-92"},"PeriodicalIF":2.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative mechanistic insights and clinical implications of the blend sign in intracerebral hemorrhage","authors":"Qian Wu ,&nbsp;Na Chen ,&nbsp;Guofeng Wu ,&nbsp;Likun Wang","doi":"10.1016/j.neuroscience.2025.07.040","DOIUrl":"10.1016/j.neuroscience.2025.07.040","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is a highly lethal subtype of stroke. The blend sign, as identified on cranial computed tomography, has demonstrated high specificity in predicting hematoma expansion and poor prognosis in patients with ICH. This radiological feature is characterized by a heterogeneous hematoma with varying densities visible on imaging. The nature of the hypodense area within the blend sign, particularly whether it represents fresh bleeding, has been a subject of debate. Recent studies have demonstrated that the hypodense region is not indicative of fresh hemorrhage as previously thought, but rather suggests the involvement of cerebrospinal fluid circulation pathways in the formation of heterogeneous hematomas. This review provides an updated overview of the mechanisms underlying the formation of the blend sign, with a particular focus on emerging research areas such as the central lymphatic system and neuroimaging techniques. We then analyze the clinical significance of the blend sign in predicting adverse outcomes and rebleeding in patients with ICH. Finally, we identify key unresolved questions related to the blend sign and propose strategic directions for future research. By addressing these critical gaps in knowledge, this review aims to enhance the current understanding of this type of heterogeneous hematoma and offer meaningful insights for its clinical diagnosis and management.</div></div>","PeriodicalId":19142,"journal":{"name":"Neuroscience","volume":"583 ","pages":"Pages 43-52"},"PeriodicalIF":2.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144749711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}