Experimental Neurology最新文献

{"title":"Neuroprotective and gut health benefits of Ugni molinae in preclinical Huntington's disease models.","authors":"Marisol Cisternas-Olmedo, Valentina Urra-Alvarez, Tomás J Huerta, Valentina Urbina-Muñoz, Barbara Saavedra, Ivania Valdés, Erick Riquelme, Mauricio Saez, Rodrigo Pérez-Arancibia, Carla Delporte, René L Vidal","doi":"10.1016/j.expneurol.2025.115406","DOIUrl":"10.1016/j.expneurol.2025.115406","url":null,"abstract":"<p><p>Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by an unstable trinucleotide CAG repeat expansion at the N-terminus of the IT-15 gene, which encodes the ∼350 kDa huntingtin protein (Htt). This mutation confers toxic properties, promoting neuronal dysfunction and death through multiple mechanisms. Effective treatments for HD are still lacking. Therefore, early-stage interventions could represent a promising approach to addressing the pathological aspects of HD. Recently, our laboratory explored the potential neuroprotective effect of murtilla (Ugni molinae, Turcz) fruit extract (ETE 19-1) in an HD cellular model and observed a significant anti-aggregation effect on mutant Htt (mHtt). In this study, we determine the beneficial effects of ETE 19-1 on HD progression in both brain and gut tissues. Our results show that a ETE 19-1 reduces motor impairment, decreases mHtt levels, and mitigates microglia activation in the striatum brain region of R6/2 mice. Moreover, we observed a reduction in gastrointestinal inflammation and an increase the gut microbiota biodiversity in R6/2 mice treated with ETE 19-1 extract. These findings highlight the impact of polyphenol-enriched natural products on the brain and gut inflammatory process during the progression of neurodegenerative diseases.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115406"},"PeriodicalIF":4.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential impact of mutant Ataxin-3 in hindbrain regions: further evidence of white matter loss as a core pathological feature.","authors":"Carina Henriques, Marta Silva, António Silva, David Rufino-Ramos, Miguel Monteiro Lopes, Romina Aron Badin, Philippe Hantraye, Luís Pereira de Almeida, Rui Jorge Nobre","doi":"10.1016/j.expneurol.2025.115413","DOIUrl":"10.1016/j.expneurol.2025.115413","url":null,"abstract":"<p><p>Spinocerebellar ataxia type 3 (SCA3) is a devastating neurodegenerative disorder that belongs to the family of polyglutamine disorders. Although the CAG repeat expansion underlying SCA3 was discovered 30 years ago, there is still no cure or treatment able to delay its progression. One of the reasons for this lag may be attributed to the phenotypic and neuropathological heterogeneity among individuals. To overcome this gap, we aimed to delve into the specific contributions of hindbrain regions that have been consistently reported to be the most degenerated in SCA3 patients, the cerebellar cortex, namely lobules IV-V, VIII and IX, deep cerebellar nuclei and the pons. For this purpose, we used lentiviral vectors to deliver the SCA3-causing gene, mutant Ataxin-3, to these specific regions in mice. We observed that the overexpression of mutant Ataxin-3 in different hindbrain regions led to the formation of Ataxin-3 aggregates in neuronal cells and mild motor impairments. Neurons in the pons were more vulnerable to mutant Ataxin-3 overexpression than in the cerebellum. There was also an increase in astrocytes and microglia recruitment that may explain myelin damage and, consequently, white matter loss in the cerebellum. Indeed, cerebellar white matter loss was the most broadly observed pathological feature upon overexpression of mutant Ataxin-3 in different regions of the hindbrain. In conclusion, we confirm that cerebellar white matter changes are a consistent feature of SCA3 neuropathology, and demonstrate that the region-specific lentiviral models offer a valuable platform to study early, selective pathological mechanisms and support future therapeutic testing.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115413"},"PeriodicalIF":4.2,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota dysbiosis exacerbates post-stroke depression via microglial NLRP3 inflammasome activation.","authors":"Yuxiao Chen, Liqiang Yu, Lulu Zhang, Cuiping Liu, Yi You, Hui Guo, Zhen Li, Xulong Yin, Ting Hong, Lidong Ding, Qi Fang","doi":"10.1016/j.expneurol.2025.115488","DOIUrl":"https://doi.org/10.1016/j.expneurol.2025.115488","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Post-stroke depression (PSD) is a neuropsychiatric complication prevalent among stroke survivors. Emerging evidence suggests that dysregulation of the microbiota-gut-brain axis is implicated in the pathogenesis of PSD. However, the exact mechanism is not clear and further research is necessary.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Initially, Sprague-Dawley (SD) rats were randomly allocated into three experimental groups: Sham, Middle Cerebral Artery Occlusion (MCAO), and PSD. Behavioral tests were conducted to evaluate depressive-like behavior. Fecal samples from all groups underwent 16S rRNA sequencing for comprehensive gut microbiota analysis. Colonic tissues were collected from rats and subjected to immunohistochemical analysis for quantification of tight junction proteins (ZO-1, Occludin, and Claudin). Peripheral blood plasma was obtained for the determination of IL-1β, IL-6, TNF-α, and IL-18 levels using enzyme-linked immunosorbent assay (ELISA). Lastly, hippocampus tissues were harvested for molecular characterization of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation and inflammatory cytokines expression through tripartite methodology: Reverse Transcription quantitative PCR (RT-qPCR), Western blot, and immunofluorescence. Concurrently, hippocampal concentrations of 5-HT, BDNF, and PSD-95 were also measured by ELISA. Subsequently, Fecal Microbiota Transplantation (FMT) was performed by administering fecal suspensions from PSD and Sham donor rats to healthy SD recipients via oral gavage. Then, use the above methods to test the same indicator.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;Comparative analyses showed that microbial species richness and diversity indices were significantly reduced in PSD model rats, along with a compositional imbalance of the gut microbiota. Concurrently, reduced expression of the colonic tight junction proteins ZO-1, Occludin, and Claudin was observed, accompanied by elevated levels of peripheral inflammatory cytokines. In PSD rats, NLRP3 inflammasome activation was detected in the ischemic hippocampus, along with increased expression of the inflammatory cytokines IL-18 and IL-1β, and decreased levels of 5-HT, BDNF, and PSD-95. Subsequently, using FMT technology, PSD rat feces were innovatively prepared into a fecal suspension and administered to healthy SD rats. Analysis revealed that FMT-PSD rats exhibited a disrupted gut microbiota structure, impaired colonic barrier integrity, activation of the hippocampal NLRP3 inflammasome, elevated inflammatory cytokine levels, and reduced neurotransmitter expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In summary, these data demonstrate that dysbiosis of the intestinal microbiota compromises gut barrier integrity and elicits systemic inflammation, which may subsequently activate the NLRP3 inflammasome in hippocampal microglia. This activation promotes the release of pro-inflammatory cytokines IL-18 and IL-1β,","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115488"},"PeriodicalIF":4.2,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network mechanisms in rapid-onset dystonia-parkinsonism.","authors":"Meret Möller, Johanna A Nieweler, Vadim V Nikulin, Christoph van Riesen","doi":"10.1016/j.expneurol.2025.115491","DOIUrl":"https://doi.org/10.1016/j.expneurol.2025.115491","url":null,"abstract":"<p><p>Rapid-onset dystonia-parkinsonism (RDP) is a rare neurological disorder caused by mutations in the ATP1A3 gene. Symptoms are characterized by a dystonia-parkinsonism. Recently, experimental studies have shown that the pathophysiology of the disease is based on a combined dysfunction of the cerebellum (CB) and basal ganglia (BG) and that blocking their interaction can alleviate the symptoms. The underlying network mechanisms have not been studied so far. Our aim was to characterize neuronal network activity in the BG and CB and motor cortex in the ouabain model of RDP by site-specific infusion of ouabain. Rats were chronically infused with ouabain either in the CB, striatum (STR) or at both places simultaneously. Motor behavior was scored using published rating systems. Parallel in vivo recordings of local field potentials (LFP) from M1, deep cerebellar nuclei (DCN) and substantia nigra reticulata (SNr) were performed. Data were compared to untreated controls. Ouabain infusion into the cerebellum produced severe dystonia that was associated with increased high-frequency gamma oscillations in the DCNs, which were subsequently transmitted to the BG and M1. Striatal infusion led to parkinsonism and elevated beta-oscillations in SNr that were transmitted to the CB and M1. The simultaneous application of STRs and CB with ouabain resulted in dystonia-parkinsonism and increased beta oscillations in BG, CB, and M1. We demonstrate that symptom-specific beta and gamma oscillations can be transmitted between the BG and CB, which is likely to be very important for the understanding of disease mechanisms.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115491"},"PeriodicalIF":4.2,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amplifying blood brain barrier injury: Neuroinflammation propagates cerebral microbleed cascades in cerebral small vessel disease, driving dementia.","authors":"Mengxin Wang, Mofan Li, Haowen Yuan, Yang Sun, Yongyue Zhang, Weiguang Zhang, Xiaolong Liang, Shumin Wang","doi":"10.1016/j.expneurol.2025.115485","DOIUrl":"https://doi.org/10.1016/j.expneurol.2025.115485","url":null,"abstract":"<p><strong>Objective: </strong>As an important cause of cognitive impairment, Cerebral Small Vessel Disease (CSVD) is characterized by structural and functional abnormalities of the Blood-Brain Barrier (BBB). To explore the association between impaired integrity of the blood-brain barrier and decline in cognitive ability, and to clarify the specific dynamic pathological and physiological changes of the model, the alterations in synaptic plasticity, as well as the specific impact of blood-brain barrier damage on neuronal function.</p><p><strong>Methods: </strong>In this study, Ultrasound-Targeted Microbubble Destruction (UTMD) technology was innovatively used to construct an animal model of CSVD. Multi-dimensional evidence such as MRI, ultrasound super resolution microvascular imaging (USRMI), molecular biology, behavior, and transcriptome sequencing was used for research.</p><p><strong>Results: </strong>This model accurately recapitulates the typical features of CSVD such as cerebral microbleeds, microinfarcts, and enlarged perivascular space, and reveals the molecular cascade mechanism of BBB damage triggering cognitive impairment. Studies have found that neuroinflammation induced by BBB leakage inhibits neuronal synaptic plasticity, in which the abnormal activation of microglia is the key node leading to the reduction of neuronal dendritic spine density and neural network dysfunction. Transcriptome sequencing results further confirmed that the activation of multiple signaling pathways promoted the occurrence of cognitive impairment in CSVD rats. This study provides a logical chain of \"BBB damage, neuroinflammation, and synaptic dysfunction\" for CSVD-related cognitive impairment, provides experimental evidence that BBB damage is the core mechanism of CSVD disease.</p><p><strong>Interpretation: </strong>These findings not only deepen the systematic understanding of the pathogenesis of CSVD, but also provide new animal models and potential therapeutic targets for translational medicine research.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115485"},"PeriodicalIF":4.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The TrkA agonist gambogic amide promotes neuroplasticity and recovery following ischemic stroke.","authors":"Shih-Yen Tsai, Elizabeth Gino, Duane Nguyen, Steven Hinton, Son T Ton, Russ P Nockels, Robert G Farrer, Gwendolyn L Kartje","doi":"10.1016/j.expneurol.2025.115487","DOIUrl":"https://doi.org/10.1016/j.expneurol.2025.115487","url":null,"abstract":"<p><p>Recovery from ischemic brain damage cause by stroke is limited unless treatments are implemented within a narrow time window to increase blood flow and reduce tissue damage to the affected area of the brain. Our laboratory has pioneered alternative approaches that are not restricted by a treatment window and involve stimulating neuroplastic mechanisms within uninjured areas of the brain to establish new compensatory neuronal connections that restore function. In this report, we tested if the small molecule TrkA agonist gambogic amide (GamAm) could stimulate neuroplasticity and recovery of function following stroke. Rats first were trained on the skilled forelimb reaching task and the horizontal ladder rung walking task and then underwent MCAO to result in an ischemic stroke in the motor cortex associated with the preferred forelimb. One week later they received four doses (one per day) of GamAm (2 mg/kg, i.p.). The rats underwent behavioral testing for eight weeks after which they received an injection of the anterograde neuronal tracer biotinylated dextran amine (BDA) into the contralesional motor cortex. Our results show that rats receiving GamAm displayed significant improvement over control vehicle-treated rats in both the skilled reaching and walking behavioral tasks. Analysis of BDA-positive axons revealed that GamAm treatment resulted in increased corticorubral plasticity to the deafferented red nucleus, an important area for motor control. These findings support a role for GamAm, and possibly other small molecule Trk agonists, as potential therapies for stimulating neuroplastic mechanisms to promote stroke recovery.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115487"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central amygdala-substantia nigra pars compacta circuit mediates anxiety- and depression-like behaviors in MPTP-treated mice.","authors":"Haixia Tang, Yiheng Li, Pengcheng Huang, Haijie Xiang, Xinyu Long, Menghua Li, Doudou Zhao, Ziye Jia, Kaiyan Jiang, Qing Li, Yuting He, Li Ying, Yuanjian Yang, Wenquan Zou, Ying Xiong, Daojun Hong","doi":"10.1016/j.expneurol.2025.115489","DOIUrl":"https://doi.org/10.1016/j.expneurol.2025.115489","url":null,"abstract":"<p><p>Parkinson's disease (PD) is characterized by progressive degeneration of substantia nigra pars compacta (SNc) dopamine (DA) neurons, leading to motor dysfunction. Non-motor symptoms of PD, such as neuropsychiatric symptoms (anxiety and depression), often precede motor symptoms and seriously affect quality of life, but the mediating mechanism has not been well understood. The SNc receives input from somatostatin (SOM) neurons in the central amygdala (CeA), which convey reward related information. This study demonstrated that optogenetic activation of CeA^SOM-SNc circuit induced real-time place preference (RTPP) and alleviated anxiety-like behaviors caused by acute stress. SOM neurons in the CeA preferentially targeted GABAergic neurons in the SNc, optogenetic activation of CeA^SOM-SNc may activate TH neurons in the SNc through disinhibition. The response of CeA neurons to reward was blunted in MPTP-treated mice, and chronic chemogenetic silencing of CeA-SNc induced anxiety- and depression-like behaviors in mice. Furthermore, chronically chemogenetic activation of CeA^SOM-SNc or DA neurons in SNc alleviated anxiety- and depression-like behaviors in MPTP-treated mice. Reward-based chocolate intervention alleviated depression-like behaviors of MPTP-treated mice. In summary, our results indicate that the CeA^SOM-SNc circuit may mediate anxiety- and depression-like behaviors by regulating the activity of SNc DA neurons.</p>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":" ","pages":"115489"},"PeriodicalIF":4.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary and exercise interventions improve cognition and alter hippocampal transcriptomics in a mouse model of the metabolic syndrome","authors":"Pongrat Jaisil ,&nbsp;Stephanie A. Eid ,&nbsp;Kai Guo ,&nbsp;Masha G. Savelieff ,&nbsp;Dae-Gyu Jang ,&nbsp;Bhumsoo Kim ,&nbsp;Crystal Pacut ,&nbsp;John M. Hayes ,&nbsp;Diana M. Rigan ,&nbsp;Andrew Carter ,&nbsp;Samuel J. Teener ,&nbsp;Haley McQuown ,&nbsp;Ian F. Webber-Davis ,&nbsp;Junguk Hur ,&nbsp;Jacob D. Meyer ,&nbsp;Eva L. Feldman","doi":"10.1016/j.expneurol.2025.115483","DOIUrl":"10.1016/j.expneurol.2025.115483","url":null,"abstract":"<div><div>Metabolic syndrome (MetS) is a major global health concern that continues to rise in prevalence and further augments disease burden by predisposing individuals to cognitive impairment (CI). Managing MetS through lifestyle habits or interventions may prevent or improve CI. The ketogenic diet (KD) has garnered interest, but its long-term efficacy in preventing CI remains unknown, as does the optimal regimen in individuals that have already developed MetS. Herein, in a preventative paradigm in mice, we evaluated the ability of relatively long-term KD to prevent CI versus a Western-style high-fat diet (HFD) that induces MetS and CI. In an intervention paradigm to mice that had already developed MetS and CI, we compared the efficacy of low-fat standard diet intervention (SDI), KD intervention (KDI), exercise intervention (EXI), and combined KD-exercise intervention (KDI-EXI). We found that KD more effectively managed metabolism and prevented CI versus HFD. Among interventions, SDI, KDI, and KDI-EXI outperformed EXI, suggesting that dietary regimens universally surpass exercise alone in ameliorating HFD-induced MetS and CI. In tandem, to gain molecular insight, we profiled gene expression, and HFD hippocampus differed from other groups particularly in metabolic and neuroactive ligand-receptor signaling pathways. Overall, our findings have important health implications and especially advocate dietary strategies for preventing or improving MetS and associated CI.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"395 ","pages":"Article 115483"},"PeriodicalIF":4.2,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian clock protein Bmal1 protects against transient focal cerebral ischemia in mice by regulating master signals controlling cell survival and metabolism","authors":"Mustafa C. Beker ,&nbsp;Elif Sertel Evren ,&nbsp;Elif Özbay ,&nbsp;Buse Balaban ,&nbsp;Enes Dogan ,&nbsp;Hayriye E. Yelkenci ,&nbsp;Nilay Ates ,&nbsp;Ahmet B. Caglayan ,&nbsp;Thorsten R. Doeppner ,&nbsp;Dirk M. Hermann ,&nbsp;Ertugrul Kilic","doi":"10.1016/j.expneurol.2025.115481","DOIUrl":"10.1016/j.expneurol.2025.115481","url":null,"abstract":"<div><div>The circadian rhythm, regulated by the suprachiasmatic nucleus through a transcription-translation feedback loop, plays a crucial role in maintaining homeostasis and optimizing physiological processes based on time of day. Recent studies have highlighted its role in cell survival under pathophysiological conditions. In this study, we explored the impact of the transcription factor Bmal1, a key clock protein, on ischemic brain injury by manipulating its expression through lentiviral vectors and <em>Bmal1</em> knockout in mice exposed to 30 min of middle cerebral artery occlusion followed by 72 h or 42 days survival. Ischemic injury was evaluated alongside proteome analyses and Western blots in the acute stroke phase at 72 h post-ischemia/reperfusion. In the long-term phase, we examined neurogenesis, gliogenesis, angiogenesis, and brain atrophy at 42 days post-ischemia/reperfusion. Our results demonstrate that <em>Bmal1</em> overexpression enhances neuronal survival and reduces cell injury in the ischemic brain, whereas <em>Bmal1</em> knockdown or knockout has opposite effects. At the molecular level, Bmal1 was found to control key signaling pathways, including the master regulator mTOR in ischemic brain tissue. Proteome analyses by LC-MS/MS showed that Bmal1 potently regulated pathways involved in oxidative phosphorylation, cell metabolism, neurodegeneration, and oxidative stress. In the long-term phase, <em>Bmal1</em> overexpression was shown to promote neurogenesis and angiogenesis, while reducing gliogenesis and glial scar formation, thereby facilitating brain recovery. These findings suggest that Bmal1 plays a pivotal role in ischemic stroke recovery, positioning it as a potential target for stroke treatment.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"395 ","pages":"Article 115481"},"PeriodicalIF":4.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetic encephalopathy models: A systematic review from cells to animals","authors":"Yongjie Xu ,&nbsp;Changyudong Huang ,&nbsp;Yiqiong Zhang ,&nbsp;Haizhi Li ,&nbsp;Huiru Yang ,&nbsp;Mi Liu ,&nbsp;Liying Zhu ,&nbsp;Chengcheng Li ,&nbsp;Yinxue Zhong ,&nbsp;Lei Tang ,&nbsp;Shuyun Zhao ,&nbsp;Wei Pan","doi":"10.1016/j.expneurol.2025.115477","DOIUrl":"10.1016/j.expneurol.2025.115477","url":null,"abstract":"<div><div>Diabetic encephalopathy, a significant complication of diabetes, is primarily characterized by cognitive dysfunction, manifesting as deficits in learning and memory. In recent years, the global rise in diabetes prevalence has been paralleled by an increase in the incidence of diabetic encephalopathy. In some patients, this condition is further aggravated by coexisting Alzheimer's disease, leading to even more pronounced cognitive decline. Despite ongoing research, the pathogenesis of diabetic encephalopathy remains largely exploratory, and the development of targeted therapies has yet to yield significant breakthroughs. A cornerstone of disease research is the use of cell and animal models, which serve to simulate the onset and progression of various conditions. To date, over ten models have been developed for the study of diabetic encephalopathy, each offering distinct advantages and limitations, and their suitability varies depending on the research context. This review examines the current cell and animal models of diabetic encephalopathy and evaluates the rationale for model selection based on different research directions and perspectives, aiming to provide a valuable reference for advancing our understanding of the disease's pathogenesis and for facilitating drug development.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"395 ","pages":"Article 115477"},"PeriodicalIF":4.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}