Frontiers in Cellular Neuroscience最新文献

{"title":"Investigation of neuromodulation of the endbulb of Held synapse in the cochlear nucleus by serotonin and norepinephrine.","authors":"Maria Groshkova, Theocharis Alvanos, Yumeng Qi, Fangfang Wang, Carolin Wichmann, Yunfeng Hua, Tobias Moser","doi":"10.3389/fncel.2025.1575158","DOIUrl":"https://doi.org/10.3389/fncel.2025.1575158","url":null,"abstract":"<p><strong>Introduction: </strong>Synapses vary greatly in synaptic strength and plasticity, even within the same circuitry or set of pre- and postsynaptic neurons. Neuromodulation is a candidate mechanism to explain some of this variability. Neuromodulators such as monoamines can differentially regulate presynaptic function and neuronal excitability. Variability is found also for the large calyceal synapses of the auditory pathway that display high synaptic vesicle (SV) release probability (P_vr) and large postsynaptic currents <i>in vitro</i> enabling reliable and temporally precise transmission of auditory information. In this study, we investigated whether the endbulb of Held synapse formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN) of mice is modulated by norepinephrine (NE) and serotonin (5-HT).</p><p><strong>Methods: </strong>We used electron microscopy (EM) of the cochlear nucleus (CN) to investigate the presence of monoaminergic projections. Furthermore, we performed immunohistochemistry to study the localization of monoamine transporters and receptors in the AVCN. We performed patch-clamp recordings from BCs to study spontaneous and evoked synaptic transmission as well as short-term plasticity of the endbulb of Held synapse and to investigate the excitability of the BCs.</p><p><strong>Results: </strong>We found EM evidence for putative monoaminergic varicosities in both ventral and dorsal divisions of the CN. Immunostaining for vesicular 5-HT and NE transporters revealed NE-containing and 5-HT-containing varicosities in the AVCN, juxtaposed to both endbulbs and BCs. Furthermore, we detected immunofluorescence for 5-HT_1B, 5-HT₄, and 5-HT₇ receptors (R) and α_2C-adrenergic receptors (AR) in BCs. Patch-clamp recordings from BCs revealed an increase in frequency of miniature excitatory postsynaptic currents (mEPSCs) upon application of NE but not 5-HT. Evoked synaptic transmission was unaffected by the application of either NE or 5-HT. Similarly, when studying the biophysical properties of the BCs, we did not observe effects of NE or 5-HT on low-voltage-activated K⁺ ( <math> <msubsup><mrow><mtext>K</mtext></mrow> <mrow><mtext>LVA</mtext></mrow> <mrow><mo>+</mo></mrow> </msubsup> </math> ) and hyperpolarization-activated mixed cation (HCN) channels during application.</p><p><strong>Discussion: </strong>In summary, we report evidence for the presence of monoaminergic innervation in the cochlear nucleus and for subtle functional NE-neuromodulation at the endbulb of Held synapse.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1575158"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting autophagy in astrocytes: a potential for neurodegenerative disease intervention.","authors":"Maja Potokar, Jernej Jorgačevski","doi":"10.3389/fncel.2025.1584767","DOIUrl":"https://doi.org/10.3389/fncel.2025.1584767","url":null,"abstract":"<p><p>Autophagy contributes to cellular homeostasis by regulating the degradation and recycling of damaged organelles and misfolded proteins. In the central nervous system (CNS), impaired autophagy contributes to inflammation, disrupts cellular metabolism, and leads to the accumulation of toxic protein aggregates that accelerate the progression of neurodegenerative diseases. In addition to its role in protein and organelle turnover, autophagy facilitates the elimination of pathogenic bacteria and viruses, whose infections can also lead to neurological diseases and neuroinflammatory processes. Astrocytes, the most abundant glial cells in the CNS, play a crucial role in maintaining neuronal homeostasis by regulating neurotransmitter balance, ion exchange, and metabolic support. During neurodegeneration, they become reactive, actively participating in neuroinflammatory responses by releasing proinflammatory cytokines, activating microglia, and removing toxic aggregates. Cytokine-mediated responses and metabolic changes in astrocytes influence neuronal viability and neurotransmission. Autophagy in astrocytes plays an important role in tuning the astrocyte-dependent activity of neurons under physiological conditions and in pathological activation of astrocytes by disease, injury or pathogenic stimuli. In this review, we highlight the contribution of astrocytes to neurodegeneration from the perspective of changes in their cytoskeleton, the autophagy process in which the cytoskeleton plays a crucial role, and the metabolic support of neurons. The modulation of autophagy at different stages has the potential to serve as an additional therapeutic target in CNS diseases.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1584767"},"PeriodicalIF":4.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The wave nature of the action potential.","authors":"Vitaly L Galinsky, Lawrence R Frank","doi":"10.3389/fncel.2025.1467466","DOIUrl":"https://doi.org/10.3389/fncel.2025.1467466","url":null,"abstract":"<p><p>An alternative to the standard Hodgkin-Huxley model for the action potential in axons is presented. It is based on our recently developed theory of electric field wave propagation in anisotropic and inhomogeneous brain tissues, which has been shown to explain a broad range of observed coherent synchronous brain electrical processes. We demonstrate that this theory also explains the spiking behavior of single neurons, thereby bridging the gap between the fundamental element of brain electrical activity-the neuron-and large-scale coherent synchronous electrical activity. We demonstrate that our recently developed theory of electric field wave propagation in anisotropic and inhomogeneous brain tissues, which has been shown to explain a broad range of observed coherent synchronous brain electrical processes, also applies to the spiking behavior of single neurons, thus bridging the gap between the fundamental element of brain electrical activity (the neuron) and large-scale coherent synchronous electrical activity. Our analysis indicates that a non-linear system with several small parameters can mathematically describe the membrane interface of the axonal cellular system. This enables the rigorous derivation of an accurate yet simpler non-linear model through the formal small-parameter expansion. The resulting action potential model exhibits a smooth, continuous transition from the linear wave oscillatory regime to the non-linear spiking regime, as well as a critical transition to a non-oscillatory regime. These transitions occur with changes in the criticality parameter and include several different bifurcation types, representative of the various experimentally detected neuron types. This new theory addresses the limitations of the Hodgkin-Huxley model, including its inability to explain extracellular spiking, efficient brain synchronization, saltatory conduction along myelinated axons, and various other observed coherent macroscopic brain electrical phenomena. We also demonstrate that our approach recovers the standard cable axon theory, utilizing the relatively simple assumptions of piece-wise homogeneity and isotropy. However, the diffusion process described by the cable equation is not capable of supporting action potential propagation across a wide range of experimentally reported axon parameters.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1467466"},"PeriodicalIF":4.2,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding serotonin: the molecular symphony behind depression.","authors":"Yue Shu, Lei Tian, Xing Wang, Tinyang Meng, Shouyang Yu, Yulan Li","doi":"10.3389/fncel.2025.1572462","DOIUrl":"https://doi.org/10.3389/fncel.2025.1572462","url":null,"abstract":"<p><p>The serotonin (5-hydroxytryptamine) system represents a crucial neurotransmitter network that regulates mood, behavior, and cognitive functions, playing a significant role in the pathogenesis and progression of depression. Although this perspective faces significant challenges, the serotonin system continues to exert substantial modulatory effects on specific aspects of psychological functioning and actively contributes to multiple pathological processes in depression development. Therefore, this review systematically integrates interdisciplinary research advances regarding the relationship between the 5-hydroxytryptamine (5-HT) system and depression. By focusing on core biological processes including serotonin biosynthesis and metabolism, SERT gene regulatory networks, and protein molecular modifications, it aims to elucidate how 5-HT system dysregulation contributes to the development of depression, while providing novel research perspectives and therapeutic targets for innovative antidepressant drug development.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1572462"},"PeriodicalIF":4.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating CD4+, CD8+, and double-negative T cells in ischemic stroke and stroke-associated infection: a prospective case-control study.","authors":"Magdalena Telec, Magdalena Frydrychowicz, Radosław Kazmierski, Izabela Wojtasz, Grzegorz Dworacki, Wojciech Kozubski, Maria Łukasik","doi":"10.3389/fncel.2025.1547905","DOIUrl":"https://doi.org/10.3389/fncel.2025.1547905","url":null,"abstract":"<p><strong>Introduction: </strong>Adaptive immunity after a stroke results in a shift of T cells between compartments, leading to peripheral lymphopenia and an increased number of T cells within the brain lesion. Stroke-associated infection (SAI) presents a clinically significant challenge in stroke units. The role of T-cell subsets in the post-stroke immune response and in SAI remains unclear. Thus, we aimed to observe the quantitative changes of circulating CD4+, CD8+, double-negative T cells, and the CD4+/CD8+ ratio in stroke and SAI.</p><p><strong>Methods: </strong>We prospectively assessed circulating CD4+, CD8+, and double-negative T cells using flow cytometry in 52 patients on days 1, 3, 10, and 90 after ischemic stroke. We compared the results to those obtained from age-, sex-, and vascular risk factor-matched controls. We analyzed lymphocyte parameters in relation to clinical outcome, SAI, infarct lesion volume, and risk factor burden.</p><p><strong>Results: </strong>There were no differences in the studied parameters between stroke patients and controls, as well as between subjects with and without SAI. A higher percentage of CD4+ T cells and a higher CD4+/CD8+ ratio correlated with better clinical status in the acute and subacute phases, while CD8+ T cells showed the opposite correlation. The percentage of CD8+ T cells positively correlated with CRP levels during the acute and subacute phases of stroke, as well as in the control group. A negative correlation was noted between the percentage of CD4+ T cells on D1 and the serum CRP level on D10 after stroke. Similarly, the CD4+/CD8+ ratio on D1 negatively correlated with CRP on D1, D3, and D10. In patients with a history of hypertension (HT), there was a higher percentage of CD8+ T cells and a lower percentage of CD4+ T cells in the acute phase of stroke than those without HT.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1547905"},"PeriodicalIF":4.2,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topographic relationship between glial cells and neovessels of the epiretinal membrane in proliferative diabetic retinopathy depends on the phase of angiogenesis.","authors":"Svetlana V Sdobnikova, Sergey S Makhotin, Alexander V Revishchin, Veronika Y Sysoeva, Galina V Pavlova, Lyubov E Sdobnikova","doi":"10.3389/fncel.2025.1571596","DOIUrl":"https://doi.org/10.3389/fncel.2025.1571596","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the topographic relationship between glial tissue and active neovessels in epiretinal membranes (ERMs) in proliferative diabetic retinopathy (PDR).</p><p><strong>Materials and methods: </strong>Phase-contrast and immunofluorescence microscopy were performed on 17 surgically removed ERMs from 17 eyes of 17 PDR patients. Clusters of active neovessels and the surrounding posterior hyaloid membrane were excised en bloc. ERMs were immunolabeled with anti-glial fibrillary acidic protein (GFAP) antibodies to identify glia, and with anti-collagen IV or anti-von Willebrand factor (VWF) antibodies to identify neovessels. All ERMs were analyzed as whole-mounted preparations, each including the area of leading neovessels.</p><p><strong>Results: </strong>GFAP-immunopositive glial cells (GCs) were identified in 11 of 17 specimens (65%). These cells also co-expressed type IV collagen. Fibrils immunopositive for type IV collagen (GFAP-negative) were detected in all cases. The topography, structure, and GFAP immunoreactivity distinguished GCs from GFAP-negative hyalocytes. GCs had bipolar shape, small cell bodies, very long, sparsely branching, bidirectional processes, and showed a tendency to form clumps. The structure of GCs was more consistent with that of Müller cells. In all ERMs, the majority of GCs were localized around the epicenter of neovascular clusters (where neovessels branched from the maternal vessel), which also corresponded to the highest density of collagen fibrils. In four cases (23.5%), GCs were also identified in the area of the leading capillaries; however, no signs of direct interaction between GCs and developing neovessels was observed in these cases.</p><p><strong>Conclusion: </strong>Our study found no evidence of direct interaction between GCs and leading neovessels in PDR, opposite to what was shown in embryonic retinal angiogenesis. The findings may suggest that the presence of GCs near the neovascular cluster epicenter and around leading capillaries reflects different phases of the proliferative process in PDR. In the first case, GFAP+ cells appear to be involved in the involution of neovessels, which occurs during vascular remodeling or regression. In the second case, when GCs were located around the leading neovessels, their proliferation was not directly related to blood vessel formation; in our opinion, these processes may represent independent events that might have common triggers.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1571596"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications.","authors":"Kunying Zhao, Yuxiao Zhang, Shuda Yang, Lirong Xiang, Shangpeng Wu, Junfang Dong, Huan Li, Haofei Yu, Weiyan Hu","doi":"10.3389/fncel.2025.1538026","DOIUrl":"https://doi.org/10.3389/fncel.2025.1538026","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is one of the most common mental health conditions, characterized by pervasive and persistent low mood, low self-esteem, and a loss of interest or pleasure in activities that are typically enjoyable. Despite decades of research into the etiology and pathophysiological mechanisms of depression, the therapeutic outcomes for many individuals remain less than expected. A promising new area of research focuses on stress-induced neuroinflammatory processes, such as the excessive activation and crosstalk of microglia and astrocytes in the central nervous system under stress, as well as elevated levels of pro-inflammatory cytokines, which are closely linked to the onset and progression of depression. This review summarizes the mechanisms through which neuroinflammation induces or promotes the development of depression, and also highlights the effective roles of small molecules with anti-inflammatory activity in the treatment of MDD. Understanding the specific mechanisms through which stress-induced neuroinflammation further impacts depression, and using technologies such as single-cell RNA sequencing to elucidate the specific subtypes and interactions of microglia and astrocytes in depression, is of great importance for developing more effective therapeutic strategies for MDD.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1538026"},"PeriodicalIF":4.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>O</i> ⁶-methylguanine DNA methyltransferase (MGMT) expression in U1242 glioblastoma cells enhances <i>in vitro</i> clonogenicity, tumor implantation <i>in vivo</i>, and <i>sensitivity</i> to alisertib-carboplatin combination treatment.","authors":"Müge Sak, Brian J Williams, Andrew J Hey, Mayur Sharma, Leslie Schier, Megan J Wilson, Mahatma Ortega, Alyssa I Lara, Mikaela N Brentlinger, Norman L Lehman","doi":"10.3389/fncel.2025.1552015","DOIUrl":"https://doi.org/10.3389/fncel.2025.1552015","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most common and aggressive primary adult CNS tumor. Increased understanding of glioma biology is needed for novel treatment strategies and maximization of current therapies. The action of the widely used antiglioma drug, temozolomide (TMZ), relies on its ability to methylate DNA guanine bases leading to DNA double strand breaks and apoptosis. However, glioma cells capable of reversing guanine methylation via the repair enzyme <i>O</i> ⁶-methylguanine DNA methyltransferase (MGMT) are resistant to TMZ. GBMs exhibiting high MGMT expression, reflected by MGMT gene promoter hypomethylation, respond poorly to both chemo- and radiation therapy. To investigate possible non-canonical biological effects of MGMT and develop a tool to investigate drug sensitivity and resistance, we generated MGMT knockout (KO) U1242 GBM cells. MGMT KO U1242 cells showed substantially increased sensitivity to TMZ <i>in vivo</i>, and unlike wildtype U1242 cells, failed to form tumors in nude mouse brains. They also showed reduced growth in soft agar, as did wildtype U1242 and additional glioma cell lines in which MGMT expression was knocked down by siRNA. MGMT thus possesses cellular functions related to tumor cell engraftment and anchorage-independent growth beyond guanine methyltransferase repair. We additionally show that the combination of the AURKA inhibitor alisertib and carboplatin selectively induces apoptosis in high MGMT expressing wildtype U1242 cells versus MGMT KO U1242 cells and extends survival of mice orthotopically implanted with wildtype U1242 cells. This or other platinum-based drug combinations may represent a potentially effective treatment approach to chemotherapy for GBM with MGMT promoter hypomethylation.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1552015"},"PeriodicalIF":4.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic palmitoylethanolamide administration <i>via</i> slow-release subcutaneous pellets promotes neuroprotection and mitigates neuroinflammation in the Tg2576 mouse model of Alzheimer's disease.","authors":"Daniel Tortolani, Davide Decandia, Giacomo Giacovazzo, Lucia Scipioni, Anna Panuccio, Francesca Ciaramellano, Fabiola Eugelio, Federico Fanti, Emanuele Claudio Latagliata, Livia La Barbera, Debora Cutuli, Dario Compagnone, Marcello D'Amelio, Roberto Coccurello, Sergio Oddi, Laura Petrosini, Mauro Maccarrone","doi":"10.3389/fncel.2025.1571428","DOIUrl":"https://doi.org/10.3389/fncel.2025.1571428","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and non-cognitive decline associated with neuropathological hallmarks, including neuroinflammation. Palmitoylethanolamide (PEA), an endogenous lipid with anti-inflammatory and neuroprotective properties, has emerged as a promising therapeutic agent in managing AD. This study investigated the therapeutic effects of chronic (6-months) PEA administration <i>via</i> subcutaneous pellet in Tg2576 mice, a validated model of AD. The impact of PEA on amyloid precursor protein (APP) processing, astrocytic activation, microglial reactivity and neuroinflammation, nitrosative stress, dendritic spine density in hippocampal CA1 pyramidal neurons, and cognitive performance was assessed. Chronic PEA treatment of Tg2576 mice increased the expression of the α-secretase ADAM9 and reduced astrogliosis. Furthermore, PEA attenuated microglia reactivity, downregulated pro-inflammatory (CXCL13, MCP-1, GCSF) and upregulated anti-inflammatory (CXC3CL1 and IL-9) cytokine expression. Chronic PEA administration also decreased protein nitrosylation, downregulated calcineurin expression, restored dendritic spine density, and improved cognitive functions. Chronic PEA administration offers a promising therapeutic approach for AD by mitigating neuroinflammation, oxidative stress, and synaptic dysfunction, ultimately leading to cognitive function restoration.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1571428"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal injury and changes of the gut microbiota after ischemic stroke.","authors":"Yang Shen, Jin Wang, Yina Li, Xianhui Kang, Lijuan Gu","doi":"10.3389/fncel.2025.1557746","DOIUrl":"https://doi.org/10.3389/fncel.2025.1557746","url":null,"abstract":"<p><p>Stroke is the second leading cause of death and the third leading cause of disability worldwide, with ischemic stroke (IS) accounting for the vast majority of cases. This paper reviews the latest research on intestinal damage, changes in the gut microbiota, and related therapeutic strategies after IS. Following IS, the integrity of the intestinal mucosal barrier is compromised, leading to increased intestinal permeability. The gut microbiota can translocate to other organs, triggering systemic immune responses that inhibit recovery after IS. Moreover, the composition and proportion of the gut microbiota change after IS. The number of beneficial bacteria decreases, whereas the number of harmful bacteria increases. The production of beneficial metabolites, such as short-chain fatty acids (SCFAs), is reduced, and the levels of harmful metabolites, such as trimethylamine N-oxide (TMAO), increase. Antibiotics after IS not only help prevent infection but also have neuroprotective effects. Although poststroke reperfusion therapy can effectively restore cerebral blood flow, it may also cause intestinal mucosal damage and gastrointestinal dysfunction. Nutritional support after IS can alter the gut microbiota structure and promote neurological recovery. Therefore, individualized treatment for IS patients is crucial. In summary, IS affects not only the brain but the entire body system, especially the gut. Intestinal damage and dysbiosis are critical in IS occurrence, development, and prognosis. By protecting the intestinal mucosa and modulating the structure of the gut microbiota, intestinal damage and related infections can be reduced, improving patient prognosis. Future research is needed to explore therapeutic methods targeting the gut microbiota, providing more comprehensive and effective treatment strategies for IS patients.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1557746"},"PeriodicalIF":4.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}