Brain Sciences最新文献

{"title":"Does Lumbar Puncture Still Have Clinical Value for Patients with Amyotrophic Lateral Sclerosis?","authors":"Federica Ginanneschi, Stefania Casali, Chiara Cioni, Delia Righi, Emanuele Emmanuello, Cecilia Toccaceli, Domenico Plantone, Nicola De Stefano","doi":"10.3390/brainsci15030258","DOIUrl":"https://doi.org/10.3390/brainsci15030258","url":null,"abstract":"<p><p><b>Background:</b> The relationship between routine cerebrospinal fluid (CSF) testing and clinical and prognostic data in amyotrophic lateral sclerosis (ALS) remains unclear. Additionally, biochemical data have never been correlated with markers of neurodegeneration. The purpose of this study is to determine whether lumbar puncture may still have clinical utility in ALS. <b>Methods:</b> We collected the CSF profiles of 140 ALS subjects. CSF protein, albumin, IgG, IgG index, albumin quotient (QAlb), t-tau, p-tau, and Aβ42 were analyzed. <b>Results:</b> Approximately one-quarter of ALS patients had elevated levels of protein, albumin, and QAlb in the CSF, but these were not associated with clinical or survival data. Among the neurodegeneration markers, the percentage of patients with abnormal values ranged from 26.3% to 35.4%. The p-tau/t-tau ratio and Aβ42 were correlated with both the ALS progression rate and the time from diagnosis to death. Aβ42 was the prognostic marker most strongly associated with survival. <b>Conclusions:</b> The lack of correlation between biochemical CSF findings and the clinical and/or prognostic status of ALS suggests that these markers have no clinical value. However, neurodegeneration markers that are easily measurable in clinical laboratories, particularly Aβ42, may be useful at the time of diagnosis for predicting ALS survival and progression rate.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728423","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":"CCR2 Regulates Referred Somatic Hyperalgesia by Mediating T-Type Ca²⁺ Channel Currents of Small-Diameter DRG Neurons in Gastric Ulcer Mice.","authors":"Ziyan Yuan, Huanhuan Liu, Zhijun Diao, Wei Yuan, Yuwei Wu, Simeng Xue, Xinyan Gao, Haifa Qiao","doi":"10.3390/brainsci15030255","DOIUrl":"https://doi.org/10.3390/brainsci15030255","url":null,"abstract":"<p><p><b>Background</b>: Referred pain frequently co-exists with visceral pain. However, the exact mechanism governing referred somatic hyperalgesia remains elusive. <b>Methods</b>: By injecting 20% acetic acid into the stomach, we established a mouse model of gastric ulcer (GU). Hematoxylin and eosin (H&E) staining was used as the evaluation criterion for the gastric ulcer model. Evan's blue (EB) and von Frey tests detected the somatic sensitized area. The DRG neurons distributed among the spinal segments of the sensitized area were prepared for biochemical and electrophysiological experiments. The CCR2 antagonist was intraperitoneally (i.p.) injected into GU mice to test the effect of blocking CCR2 on somatic neurogenic inflammation. <b>Results</b>: GU not only instigated neurogenic plasma extravasation and referred somatic allodynia in the upper back regions spanning the T9 to T11 segments but also augmented the co-expression of T-type Ca²⁺ channels and CCR2 and led to the gating properties of T-type Ca²⁺ channel alteration in T9-T11 small-diameter DRG neurons. Moreover, the administration of the CCR2 antagonist inhibited the T-type Ca²⁺ channel activation, consequently mitigating neurogenic inflammation and referred somatic hyperalgesia. The application of the CCR2 agonist to normal T9-T11 small-diameter DRG neurons simulates the changes in the gating properties of T-type Ca²⁺ channel that occur in the GU group. <b>Conclusions</b>: Therefore, these findings indicate that CCR2 may function as a critical regulator in the generation of neurogenic inflammation and mechanical allodynia by modulating the gating properties of the T-type Ca²⁺ channels.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727964","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":"The Impact of Walking on BDNF as a Biomarker of Neuroplasticity: A Systematic Review.","authors":"Mohamed Hesham Khalil","doi":"10.3390/brainsci15030254","DOIUrl":"https://doi.org/10.3390/brainsci15030254","url":null,"abstract":"<p><strong>Background/objectives: </strong>The brain-derived neurotrophic factor (BDNF) is a critical exercise-induced modulator of various neuroplasticity processes, including adult hippocampal neurogenesis. Environmental affordance for physical activity is a novel theory that aims to increase the BDNF through walking or climbing stairs, stimulated by the urban and interior environment. In a systematic review, this paper explores the association between walking, as a structured or free-living form of physical activity, and changes in the BDNF in humans with healthy locomotion.</p><p><strong>Method: </strong>A systematic review with a registered protocol, INPLASY2024110093, and following the PRISMA guidelines, includes English-language original research articles on adult and older adult human subjects who are locomotor-healthy, studies on walking as a structured exercise or free-living physical activity that is presented in a non-combined intervention, and must report changes in the BDNF as a dependent variable. The search was conducted using three databases: PubMed, Web of Science, and Scopus, resulting in 21 eligible studies.</p><p><strong>Results: </strong>This systematic review finds that the impact of walking on the BDNF is evidenced, but subject to moderate to high intensities in single bouts. At the same time, the long-term effects are yet to be fully understood, potentially due to the uptake of the BDNF for functional brain improvements, neuroplasticity processes, or muscle repair, instead of an accumulation of the BDNF itself, yet still confirm the important role of the BDNF for neurosustainability. Age and environmental factors such as heat are also found to affect the increase in the BDNF. The narrative synthesis provides elaborate explanations for understanding those complex dynamics before reaching future conclusions on the impact of walking or environmental affordance for physical activity on the changes in the BDNF concentrations.</p><p><strong>Conclusions: </strong>This systematic review highlights the potential role played by moderate- and high-intensity walking as a lifestyle intervention that can be utilised through the built environment to promote adaptive brain changes, through the sustainable regulation of the BDNF.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728465","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":"Conditioning Electrical Nerve Stimulation Enhances Functional Rewiring in a Mouse Model of Nerve Transfer to Treat Chronic Spinal Cord Injury.","authors":"Juan Sebastián Jara, Marwa A Soliman, Amanda Bernstein, Paola di Grazia, Adam R Ferguson, Justin M Brown, Abel Torres-Espín, Edmund R Hollis","doi":"10.3390/brainsci15030251","DOIUrl":"https://doi.org/10.3390/brainsci15030251","url":null,"abstract":"<p><strong>Background/objectives: </strong>Nerve transfer surgery is a state-of-the-art surgical approach to restore hand and arm function in individuals living with tetraplegia, significantly impacting daily life. While nearly a third of all individuals with chronic spinal cord injury may benefit from this intervention, variability in outcomes can limit the functional impact. A bedside to bench approach was taken to address the variable response of tetraplegic individuals to nerve transfer surgery.</p><p><strong>Methods: </strong>We used a hierarchical multiple factor analysis to evaluate the effects of conditioning electrical stimulation (CES) on outcomes in a mouse model of nerve transfer to treat chronic cervical spinal cord injury.</p><p><strong>Results: </strong>We found that CES of donor nerves one week prior to nerve transfer surgery enhanced anatomical and functional measures of innervation of targeted muscles. Furthermore, CES increased the rate of recovery of naturalistic behavior.</p><p><strong>Conclusions: </strong>While the model has some limitations due to the small size of the rodent, our results support the use of CES as an effective approach to improve outcomes in clinical nerve repair settings.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728435","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":"Unveiling the Important Role of Gut Microbiota and Diet in Multiple Sclerosis.","authors":"Amina Džidić Krivić, Emir Begagić, Semir Hadžić, Amir Bećirović, Emir Bećirović, Harisa Hibić, Lejla Tandir Lihić, Samra Kadić Vukas, Hakija Bečulić, Tarik Kasapović, Mirza Pojskić","doi":"10.3390/brainsci15030253","DOIUrl":"https://doi.org/10.3390/brainsci15030253","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), characterized by neurodegeneration, axonal damage, demyelination, and inflammation. Recently, gut dysbiosis has been linked to MS and other autoimmune conditions. Namely, gut microbiota has a vital role in regulating immune function by influencing immune cell development, cytokine production, and intestinal barrier integrity. While balanced microbiota fosters immune tolerance, dysbiosis disrupts immune regulation, damages intestinal permeability, and heightens the risk of autoimmune diseases. The critical factor in shaping the gut microbiota and modulating immune response is diet. Research shows that high-fat diets rich in saturated fats are associated with disease progression. Conversely, diets rich in fruits, yogurt, and legumes may lower the risk of MS onset and progression. Specific dietary interventions, such as the Mediterranean diet (MD) and ketogenic diet, have shown potential to reduce inflammation, support neuroprotection, and promote CNS repair. Probiotics, by restoring microbial balance, may also help mitigate immune dysfunction noted in MS. Personalized dietary strategies targeting the gut microbiota hold promise for managing MS by modulating immune responses and slowing disease progression. Optimizing nutrient intake and adopting anti-inflammatory diets could improve disease control and quality of life. Understanding gut-immune interactions is essential for developing tailored nutritional therapies for MS patients.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728521","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":"Multimodal Morphometric Similarity Network Analysis of Autism Spectrum Disorder.","authors":"Antonio Del Casale, Darvin Shehu, Maria Camilla Rossi-Espagnet, Clarissa Zocchi, Irene Bilotta, Jan Francesco Arena, Alessandro Alcibiade, Barbara Adriani, Daniela Longo, Carlo Gandolfo, Andrea Romano, Stefano Ferracuti, Alessandro Bozzao, Antonio Napolitano","doi":"10.3390/brainsci15030247","DOIUrl":"https://doi.org/10.3390/brainsci15030247","url":null,"abstract":"<p><p><b>Background</b>: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by persistent difficulties in social interaction, communication, and repetitive behaviors. Neuroimaging studies have revealed structural and functional neural changes in individuals with ASD compared to healthy subjects. <b>Objectives</b>: This study aimed to investigate brain network structural connectivity in ASD using Morphometric Similarity Network (MSN) analysis. <b>Methods</b>: Data from the Autism Brain Imaging Data Exchange (ABIDE) were analyzed, comprising 597 individuals with ASD and 644 healthy controls. Structural connectivity was assessed using cortical morphometric features. Global and regional network indices, including the density index, node degree, node strength, and clustering coefficients, were evaluated. <b>Results</b>: Among the global network indices, when using a threshold value of 0.4, ASD patients compared to HCs showed a lower density (<i>p</i> = 0.041) and higher negative clustering (<i>p</i> = 0.0051) coefficients. For regional network indices, ASD patients showed a lower bilateral superior frontal cortices degree (left hemisphere: <i>p</i> = 0.014; right hemisphere: <i>p</i> = 0.0038) and strength (left: <i>p</i> = 0.017; right: <i>p</i> = 0.018). Additionally, they showed higher negative clustering coefficients in the bilateral superior frontal cortices (left, <i>p</i> = 0.0088; right, <i>p</i> = 0.0056) and bilateral pars orbitalis (left, <i>p</i> = 0.016; right, <i>p</i> = 0.0006), as well as lower positive clustering in the bilateral frontal pole (left, <i>p</i> = 0.03; right, <i>p</i> = 0.044). <b>Conclusions</b>: These findings highlight significant alterations in both global and regional brain network organization in ASD, which may contribute to the disorder's cognitive and behavioral manifestations. Future studies are needed to investigate the pathophysiological mechanisms underlying these structural connectivity changes, to inform the development of more targeted and individualized therapeutic interventions for individuals with ASD.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728428","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":"Phylogeny and Molecular Characterisation of <i>PRNP</i> in Red-Tailed Phascogale (<i>Phascogale calura</i>).","authors":"Krisel De Dios, Sachin Kumar, Ehsan Alvandi, Utpal Kumar Adhikari, Monique Amtoinette David, Mourad Tayebi","doi":"10.3390/brainsci15030250","DOIUrl":"https://doi.org/10.3390/brainsci15030250","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background/Objectives&lt;/b&gt;: The normal cellular prion protein (PrP&lt;sup&gt;C&lt;/sup&gt;) is a cell-surface glycoprotein, mainly localised in neurons of the central nervous system (CNS). The human &lt;i&gt;PRNP&lt;/i&gt; gene encodes 253 amino acid residues of precursor PrP&lt;sup&gt;C&lt;/sup&gt;. Several studies that investigated the role of &lt;i&gt;PRNP&lt;/i&gt; and PrP&lt;sup&gt;C&lt;/sup&gt; in placental mammals, such as humans and mice, failed to reveal its exact function. &lt;b&gt;Methods&lt;/b&gt;: In this study, we sequenced and characterised the &lt;i&gt;PRNP&lt;/i&gt; gene and PrP&lt;sup&gt;C&lt;/sup&gt; of the marsupial, &lt;i&gt;P. calura&lt;/i&gt;, as a strategy to gain molecular insights into its structure and physicochemical properties. Placentals are separated from marsupials by approximately 125 million years of independent evolution. &lt;b&gt;Results&lt;/b&gt;: Standard Western blotting analysis of PrP&lt;sup&gt;C&lt;/sup&gt; phascogale displayed the typical un-, mono-, and di-glycosylated bands recognized in placentals. Furthermore, we showed that phascogale &lt;i&gt;PRNP&lt;/i&gt; gene has two exons, similar to all the marsupials and placentals of the &lt;i&gt;PRNP&lt;/i&gt; genes studied. Of note, the phascogale &lt;i&gt;PRNP&lt;/i&gt; gene contained distinctive repeats in the PrP&lt;sup&gt;C&lt;/sup&gt; tail region comparable to the closely related Tasmanian devil (&lt;i&gt;Sarcophilus harrisii&lt;/i&gt;) and more distantly related to the grey short-tailed opossum (&lt;i&gt;Monodelphis domestica&lt;/i&gt;), common wombat (&lt;i&gt;Vombatus ursinus&lt;/i&gt;), and Tammar wallaby (&lt;i&gt;Macropus eugenii&lt;/i&gt;); however, its specific composition and numbers were different from placentals. Of importance, comparisons of the phascogale's PrP&lt;sup&gt;C&lt;/sup&gt; physicochemical properties with other monotremes, marsupials, and placentals confirmed the Monotremata-Marsupialia-Placentalia evolutionary distance. We found that the protein instability index, a method used to predict the stability of a protein in vivo (Stable: &lt;40; Instable &gt;40), showed that the PrP&lt;sup&gt;C&lt;/sup&gt; of all marsupials tested, including phascogale, were highly stable compared with the birds, reptiles, amphibians, and fish that were shown to be highly unstable. However, the instability index predicted that all placental species, including human (&lt;i&gt;Homo sapiens&lt;/i&gt;), mouse (&lt;i&gt;Mus musculus&lt;/i&gt;), bank vole (&lt;i&gt;Myodes glareolus&lt;/i&gt;), rhinoceros (&lt;i&gt;Rhinocerotidae&lt;/i&gt;), dog (&lt;i&gt;Canis lupus familiaris&lt;/i&gt;), flying fox (&lt;i&gt;Pteropus vampyrus&lt;/i&gt;), whale (&lt;i&gt;Physeter catodon&lt;/i&gt;), cattle (&lt;i&gt;Bos taurus&lt;/i&gt;), and sheep (&lt;i&gt;Ovis aries&lt;/i&gt;), were either slightly unstable or nearly unstable. Further, our analysis revealed that despite their predicted high PrP&lt;sup&gt;C&lt;/sup&gt; stability, &lt;i&gt;P. calura&lt;/i&gt; exhibited substantial N-terminal disorder (53.76%), while species with highly unstable PrP&lt;sup&gt;C&lt;/sup&gt;s based on their instability index, such as Danio rerio, Oryzias latipes, and Astyanax mexicanus, displayed even higher levels of N-terminal disorder (up to 75.84%). These findings highlight a discrepancy between overall predicted stability and N-terminal disorder, suggesting a potential co","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728503","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":"The Role of Well-Being, Divergent Thinking, and Cognitive Reserve in Different Socio-Cultural Contexts.","authors":"Francesca Garau, Alessandro Antonietti, Natale Salvatore Bonfiglio, Beatrice Madeddu, Maura Crepaldi, Jessica Giannì, Giulia Fusi, Laura Colautti, Virginia Maria Borsa, Massimiliano Palmiero, Maria Luisa Rusconi, Maria Pietronilla Penna","doi":"10.3390/brainsci15030249","DOIUrl":"https://doi.org/10.3390/brainsci15030249","url":null,"abstract":"<p><strong>Background: </strong>Many protective factors promote psychological well-being (PWB) in the elderly and contribute to healthy aging, such as engagement, positive emotions, and cognitive reserve (CR), which includes education, leisure, and work activities. CR sustains cognitive functioning and positively correlates with creativity, particularly divergent thinking (DT), helping older adults cope with everyday challenges and enhancing their PWB.</p><p><strong>Objectives: </strong>The present study aimed to investigate the relationships between DT, CR, PWB, memory functions, depression, stress, and anxiety indexes even in the Blue Zone (BZ), an area known for extraordinary longevity and high PWB.</p><p><strong>Methods: </strong>A total of 165 Italian healthy older adults (Mage = 73.8, SD = 6.7) from Milan (MI), Bergamo (BG), Cagliari (CA), and BZ were enrolled and divided into four groups according to their origin. Generalized linear models (GLMs) with normal and gamma link functions were used.</p><p><strong>Results: </strong>BZ presented higher DT and PWB indices than the cities but lower CR, particularly in education.</p><p><strong>Conclusions: </strong>This study highlights the influence of DT in supporting cognitive functions and PWB, suggesting that PWB and DT are key protective factors in aging.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728474","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":"Hypoxic Neuroinflammation in the Pathogenesis of Multiple Sclerosis.","authors":"Bethany Y A Hollingworth, Patrick N Pallier, Stuart I Jenkins, Ruoli Chen","doi":"10.3390/brainsci15030248","DOIUrl":"https://doi.org/10.3390/brainsci15030248","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheath around the central nervous system axons, leading to neurological dysfunction. Although the initial damage is driven by inflammation, hypoxia has been reported in several brain regions of MS patients, but the significance of this for prognosis and treatment remains unclear. Neuroinflammation can induce hypoxia, and hypoxia can induce and exacerbate neuroinflammation, forming a vicious cycle. Within MS lesions, demyelination is often followed by remyelination, which may restore neurological function. However, demyelinated axons are vulnerable to damage, which leads to the accumulation of the permanent neurological dysfunction typical in MS, with this vulnerability heightened during hypoxia. Clinically approved therapies for MS are immunomodulatory, which can reduce relapse frequency/severity, but there is a lack of pro-regenerative therapies for MS, for example promoting remyelination. All tissues have protective responses to hypoxia, which may be relevant to MS lesions, especially during remyelinating episodes. When oxygen levels are reduced in the brain, constitutively expressed hypoxia-inducible factors (HIF) are stabilised, upregulating hundreds of genes, including neuroprotective factors. Furthermore, astrocytes upregulate heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) in the early stage of MS. HB-EGF promotes protective mechanisms and induces oligodendrocyte and neuron differentiation and survival. This review article outlines the neuroinflammation and hypoxia cycle in MS pathology and identifies potential therapeutic targets to limit neurodegeneration and/or promote regeneration. Both HIF and HB-EGF signalling pathways induce endogenous protection mechanisms in the CNS, promoting neuroprotection and remyelination directly, but also indirectly by modulating the immune response in MS. Promoting such endogenous protective signalling pathways could be an effective therapy for MS patients.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728604","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":"Improving Stuttering Through Augmented Multisensory Feedback Stimulation.","authors":"Giovanni Muscarà, Alessandra Vergallito, Valentina Letorio, Gaia Iannaccone, Martina Giardini, Elena Randaccio, Camilla Scaramuzza, Cristina Russo, Maria Giovanna Scarale, Jubin Abutalebi","doi":"10.3390/brainsci15030246","DOIUrl":"https://doi.org/10.3390/brainsci15030246","url":null,"abstract":"<p><strong>Background/objectives: </strong>Stuttering is a speech disorder involving fluency disruptions like repetitions, prolongations, and blockages, often leading to emotional distress and social withdrawal. Here, we present Augmented Multisensory Feedback Stimulation (AMFS), a novel personalized intervention to improve speech fluency in people who stutter (PWS). AMFS includes a five-day intensive phase aiming at acquiring new skills, plus a reinforcement phase designed to facilitate the transfer of these skills across different contexts and their automatization into effortless behaviors. The concept of our intervention derives from the prediction of the neurocomputational model Directions into Velocities of Articulators (DIVA). The treatment applies dynamic multisensory stimulation to disrupt PWS' maladaptive over-reliance on sensory feedback mechanisms, promoting the emergence of participants' <i>natural voices</i>.</p><p><strong>Methods: </strong>Forty-six PWS and a control group, including twenty-four non-stuttering individuals, participated in this study. Stuttering severity and physiological measures, such as heart rate and electromyographic activity, were recorded before and after the intensive phase and during the reinforcement stage in the PWS but only once in the controls.</p><p><strong>Results: </strong>The results showed a significant reduction in stuttering severity at the end of the intensive phase, which was maintained during the reinforcement training. Crucially, worse performance was found in PWS than in the controls at baseline but not after the intervention. In the PWS, physiological signals showed a reduction in activity during the training phases compared to baseline.</p><p><strong>Conclusions: </strong>Our findings show that AMFS provides a promising approach to enhancing speech fluency. Future studies should clarify the mechanisms underlying such intervention and assess whether effects persist after the treatment conclusion.</p>","PeriodicalId":9095,"journal":{"name":"Brain Sciences","volume":"15 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728457","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}