Brain disorders (Amsterdam, Netherlands)最新文献

{"title":"Role of calcineurin and ionotropic glutamate receptors in Alzheimer's disease: A systematic review","authors":"Awgichew Behaile Teklemariam ,&nbsp;Edgeit Abebe Zewde ,&nbsp;Melaku Mekonnen Agidew ,&nbsp;Sisay Ayalkibet Siyamrew ,&nbsp;Lemlemu Maru ,&nbsp;Zelalem Tilahun Muche","doi":"10.1016/j.dscb.2025.100218","DOIUrl":"10.1016/j.dscb.2025.100218","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral changes. Calcineurin (CaN), a calcium/calmodulin-dependent serine/threonine phosphatase, is hyperactivated in AD, leading to enhanced neuroinflammation, synaptic dysfunction, and tau hyperphosphorylation. Similarly, the dysregulation of ionotropic glutamate receptors (iGluRs), particularly NMDA receptors in the context of AD, aggravates excitotoxicity, which in turn contributes to neuronal damage and cognitive deficits. Moreover, AMPA and kainate receptors also play significant roles in synaptic plasticity and neurodegeneration.</div><div>The intricate interplay between CaN and iGluRs, specifically NMDA, AMPA, and kainate receptors, through various signaling pathways plays a crucial role in AD pathogenesis. Therapeutic approaches targeting the CaN-iGluR axis, including CaN inhibitors and iGluR modulators, have the potential to mitigate the progression of AD and improve cognitive functions associated with the disease.</div><div>This systematic review aims to consolidate current knowledge on the molecular mechanisms underlying CaN and iGluR dysregulation in AD and discuss their potential as therapeutic targets. Future investigations should prioritize elucidating the precise interactions between CaN and iGluRs, as well as developing selective modulators to enhance the efficacy and safety of therapeutic interventions for AD.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100218"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-perinatal hypoxic ischemic encephalopathy – Long term outcome and clinico-radiological correlation","authors":"Saraswathi Ramanathan ,&nbsp;Prince Thakkar ,&nbsp;Harshad Vanjare ,&nbsp;Raji Thomas ,&nbsp;George Tharion ,&nbsp;Bijesh Yadav","doi":"10.1016/j.dscb.2025.100217","DOIUrl":"10.1016/j.dscb.2025.100217","url":null,"abstract":"<div><h3>Objective</h3><div>To study the long-term outcome of non-perinatal Hypoxic Ischemic Encephalopathy (HIE) and to co-relate clinical outcomes with neuroimaging findings.</div></div><div><h3>Materials and Methods</h3><div>Retrospective chart review and telephonic follow up study.</div><div>Family members of 72 patients, out of 101 screened patients (admitted to an inpatient rehabilitation facility with diagnosis of “HIE” within 6 months of hypoxic insult) were contactable and current telephonic modified Rankin Scale (mRS) was documented. mRS of 0–3 was considered as favorable clinical outcome and mRS of 4–6 as poor outcome. Neuroimaging (CT and MRI) were reviewed by a neuro-radiologist.</div></div><div><h3>Results</h3><div>The mean (SD) age was 34.06 (18.33) years. One year survival rate was 84.7 % (61/72 patients), with severe disability (mRS 5) in 78.6 % (<em>n</em> = 48) of survivors. At follow up, 60 patients (83.3 %) had poor outcome (mRS 6, 38.9 %, <em>n</em> = 28; mRS 5, 31.9 %, <em>n</em> = 23; mRS 4, 12.5 %, <em>n</em> = 9) and 12 patients (16.7 %) had favorable clinical outcome (mRS 2 and 3). Patients with favorable outcomes had normal imaging or subcortical involvement without diffusion restriction. Diffuse cortical and deep grey involvement, diffuse cortical white matter involvement, cerebellar involvement and brain stem involvement had worse prognosis.</div></div><div><h3>Conclusion</h3><div>HIE has an overall poor outcome in 83.3 % of the patients. Focal findings on MRI may have a slightly better prognosis than diffuse findings.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100217"},"PeriodicalIF":0.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-onset oculogyric crises in an infant with self-limited familial neonatal epilepsy : A case report","authors":"Alise Skoromka ,&nbsp;Sandis Kovaļovs","doi":"10.1016/j.dscb.2025.100215","DOIUrl":"10.1016/j.dscb.2025.100215","url":null,"abstract":"<div><h3>Background</h3><div>Oculogyric crises have been less commonly reported in KCNQ2-related disorders. This case report aims to illustrate the clinical variability of KCNQ2-related disorders and emphasize the importance of genetic diagnostics in neonatal epilepsy.</div></div><div><h3>Objective</h3><div>To present a unique case of self-limited familial neonatal epilepsy associated with an inherited KCNQ2 mutation, highlighting the occurrence of oculogyric crises.</div></div><div><h3>Methods</h3><div>Clinical evaluation, electroencephalography, magnetic resonance imaging, and genetic testing via whole-exome sequencing was utilized.</div></div><div><h3>Results</h3><div>A female infant exhibited early-onset seizures and atypical oculogyric crises. Genetic analysis revealed a pathogenic KCNQ2 duplication inherited from the mother. Treatment with valproic acid led to seizure control, and follow-up demonstrated normal psychomotor development.</div></div><div><h3>Conclusion</h3><div>This case underscores the phenotypic variability of KCNQ2-related disorders and the role of genetic testing in refining diagnosis and management.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100215"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143740030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of phytochemical composition of aqueous extract of Annona reticulata and assessment of its neuroprotective activity on Paraquat-induced neurodegeneration in Drosophila melanogaster Oregon R","authors":"Shubha,&nbsp;Vaibhavi Bhardwaj,&nbsp;Naomi Varghese,&nbsp;Sowmya Kumar","doi":"10.1016/j.dscb.2025.100214","DOIUrl":"10.1016/j.dscb.2025.100214","url":null,"abstract":"<div><div>Neurons are essential for maintaining physiological balance, and abnormalities in neuronal activity or communication can lead to medical disorders. The term “neurodegenerative diseases” refers to a broad category of neurological disorders that affect different subsets of neurons in different functional anatomical systems. The term “neurodegenerative diseases” refers to a broad category of neurological disorders that affect different subsets of neurons in different functional anatomical systems. The Oregon R strain of <em>Drosophila melanogaster</em> was used in the study to examine the neuroprotective effects of <em>Annona reticulata</em> Linn. leaf extract against Paraquat-induced neurotoxicity. As per the results of the phytochemical analysis, the Annona reticulata Linn aqueous leaf extract included many phytochemicals like flavanones, phenols, steroids, quinones, coumarins, and flavonoids. Pursuit a toxicity test on the <em>Drosophila melanogaster</em> Oregon R strain, the aqueous extract's antioxidant and neuroprotective activities were evaluated after choosing the ideal paraquat concentration to cause neurodegeneration in the flies. The extract improved the survival rates and greatly decreased locomotor impairment in the treated flies. Additionally, it demonstrated beneficial modulatory effects on the activity of antioxidant enzymes as well as ameliorative effects on the levels of oxidative stress indicators. However, further study is needed to fully understand the molecular pathways behind the extract's neuroprotective activity and to investigate its potential applicability as a medication.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100214"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effectiveness of the Halliwick concept hydrotherapy and Bobath (Neurodevelopmental Treatment-NDT) in the treatment of children with cerebral palsy–A randomised controlled trial","authors":"Konstantinos Chandolias ,&nbsp;Eleni Argyroula Tsounia ,&nbsp;Nikolaos Strimpakos ,&nbsp;Efthalia Zogka ,&nbsp;Thomas Besios ,&nbsp;Georgios Marios Kyriakatis ,&nbsp;Panagiotis Tsimeas ,&nbsp;Athanasios Tsiokanos","doi":"10.1016/j.dscb.2025.100213","DOIUrl":"10.1016/j.dscb.2025.100213","url":null,"abstract":"<div><h3>Background</h3><div>Children with cerebral palsy (CP) often face challenges in motor function, balance, and daily activities. While land-based therapies such as the Bobath concept are widely used, complementary water-based therapies, including the Halliwick concept, offer unique opportunities to enhance rehabilitation outcomes.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the effectiveness of Halliwick concept hydrotherapy on gross motor function, balance, speed, and daily life skills in children with CP. A secondary objective was to compare the combined intervention of Halliwick hydrotherapy and Bobath therapy (NDT) with Bobath therapy (NDT)alone.</div></div><div><h3>Methods</h3><div>A total of 80 children with CP (mean age: 7.53 years) participated in this 9-month long randomised controlled trial. Participants were divided into three groups: the intervention group (<em>n</em> = 40), which received one session per week of both Halliwick hydrotherapy and Bobath therapy; control group 1 (<em>n</em> = 35), which received two sessions of Bobath therapy (NDT)per week; and control group 2 (<em>n</em> = 5), which did not receive any intervention. Two-way repeated measures ANOVA was conducted to compare the GMFM, PEDI, PBS, and TUG between time and groups, while a paired <em>t</em>-test to assess water-based (WOTA 1 &amp; 2, SWIM, HAAR) through time.</div></div><div><h3>Results</h3><div>Statistically significant improvements were observed in the intervention group when compared with control groups across all measures. The intervention group demonstrated greater gains in gross motor function, balance, daily activities, and speed, using the TUG test, compared to control group 1, with minimal changes observed in control group 2. Notable improvements included increased GMFM scores (6points improvement in the intervention group compared to 3.36 in control group 1(Wilks's Lambda = 0.807, <em>F</em> = 9.222, partial η² = 0.193, <em>p</em> &lt; 0.001)), balance (PBS: +3.8 points(Wilks's Lambda = 0.778, <em>F</em> = 11.002, partial η² = 0.222, <em>p</em> &lt; 0.001)), and daily activities (PEDI: +6.32 points(Wilks's Lambda = 0.849, <em>F</em> = 6.854, partial η² = 0.151, <em>p</em> = 0.002)). Water-based assessments further highlighted substantial improvements in aquatic skills.</div></div><div><h3>Conclusion</h3><div>Incorporating Halliwick hydrotherapy into rehabilitation programs for children with CP yields significant benefits, enhancing motor skills, balance, and daily functioning beyond what is achieved with land-based interventions alone. These findings highlight the importance of integrating complementary aquatic therapies into routine clinical practice for children with CP. Further research with larger, homogeneous samples and extended intervention durations is recommended to refine these therapeutic approaches.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100213"},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of cerebellar and basal ganglia pathology on the coordination of bilateral arm movements","authors":"Chang-Ha Im ,&nbsp;Jinsung Wang ,&nbsp;Yong-Gwan Song","doi":"10.1016/j.dscb.2025.100211","DOIUrl":"10.1016/j.dscb.2025.100211","url":null,"abstract":"<div><div>The objective of this study was to compare coordination deficits between Parkinson's disease (PD) and cerebellar dysfunction (CD) patients during in- and anti-phase bilateral movements with their forearms. 48 participants were divided into four groups: recently diagnosed (de novo) PD patients; PD patients with an advanced stage of the disease; CD patients; age-matched controls. All participants performed in-phase and anti-phase bilateral coordination movements at two pacing frequencies (1 and 1.55 Hz). For interlimb coordination, relative phasing accuracy was measured; for individual limb movements, oscillation frequency, movement amplitude and harmonicity (smoothness) of each limb movement were examined. Results indicated that advanced PD patients showed larger relative phasing deviations than all other groups, but only at the higher pacing frequency in the anti-phase mode; de novo PD and CD patients were not different from controls. Regarding oscillation frequency, no patient group could move in synchrony with required pacing frequency as well as the controls. Both controls and CD patients tended to overshoot the target, while both PD groups undershot the target. In terms of movement smoothness, CD patients were the worst. These findings suggest that the basal ganglia and the cerebellum pathology may affect bilateral coordination differently: motor deficits observed during bilateral coordination tasks in PD patients may be related more directly to the deficits in interlimb coordination, while those observed in CD patients may be related more to the deficits in inter-joint coordination within each limb, which in turn may affect interlimb coordination during bilateral tasks.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine-induced behavioral perturbations, redox imbalances, and neurotransmitter deficits in mice: The preventive and reversal neuromodulatory potential of diosmin as an antipsychotic","authors":"Aya-Ebi Okubo Eneni ,&nbsp;Benneth Ben-Azu ,&nbsp;Abayomi Mayowa Ajayi ,&nbsp;Adegbuyi Oladele Aderibibge","doi":"10.1016/j.dscb.2025.100210","DOIUrl":"10.1016/j.dscb.2025.100210","url":null,"abstract":"<div><div>Schizophrenia is a major neuropsychiatric disorder associated with neurochemical perturbations characterized by behavioral abnormalities, for which effective treatment remains elusive. The current study investigated the neurotransmitter modulatory effect of diosmin in preventing and reversing ketamine-induced neurochemical and oxidative perturbations in mice. In the preventive study, mice were first treated with diosmin (50 mg/kg, i.p.) or risperidone (0.5 mg/kg) for 14-days before ketamine (20 mg/kg, i.p.) administration from the 8th-14th day. However, in the reversal approach, mice were injected with ketamine (20 mg/kg, i.p.) for 14 days before treatment with diosmin (50 mg/kg, i.p.) or risperidone from days 8–14. Behavioral consequences were measured using open-field, Y-maze, forced-swim, and social interaction tests. Neurochemical and oxidative changes critical to the disease were characterized in the striatum, prefrontal cortex and hippocampus. Diosmin improved the behavioral abnormalities and improved memory in ketamine-treated mice. Also, diosmin prevented and reversed ketamine-induced oxidative stress, evidenced by increased glutathione and superoxide-dismutase with a profound decrease in malondialdehyde levels in the striatum, prefrontal-cortex and hippocampus. Additionally, diosmin reduced nitrite levels in the striatum in the preventive approach, but with a significant decrease in the striatum and prefrontal-cortex compared to ketamine groups. Ketamine-induced increased acetylcholinesterase activity in the hippocampus and prefrontal-cortex were both prevented and reversed significantly. Lastly, ketamine-induced dopamine, serotonin and glutamate dysregulations in the striatum, prefrontal-cortex and hippocampus were prevented and reversed by diosmin compared to ketamine controls. Conclusively, diosmin improved ketamine-induced neurobehavioral deficits by augmenting antioxidant systems and modulating neurotransmitters in mice brains.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of ferroptosis pathways in Huntington's disease: Insight of pathophysiology to emerging treatment","authors":"Mohd Haris Jamal ,&nbsp;Meghna Dhupar ,&nbsp;Khadga Raj Aran","doi":"10.1016/j.dscb.2025.100207","DOIUrl":"10.1016/j.dscb.2025.100207","url":null,"abstract":"<div><div>Huntington's disease (HD) is a persistent ailment identified by progressive physical disability, cognitive impairment, and severe psychiatric symptoms. A mutation in the HTT gene is at the root of HD, causing the development of a protein known as mutant huntingtin (mHTT), which wreaks havoc on neuronal health. While oxidative stress and altered iron metabolism have long been associated with HD, new research has shown a novel and intriguing mechanism: ferroptosis. This sort of regulated cell death is caused by iron-dependent lipid peroxidation and evidence suggests that it plays an important role in HD's severe neurodegeneration. mHTT exacerbates oxidative damage and promotes ferroptosis by disrupting iron homeostasis and antioxidant defenses. HD models and patient tissues exhibit enhanced lipid peroxidation, iron overload, and evidence of ferroptotic cell death, indicating ferroptosis as a major contribution to disease pathophysiology. Even more promising is that blocking ferroptosis can save neurons and enhance outcomes in preclinical HD models. This discovery provides a tantalizing view into prospective medicines that could halt or reduce disease development, a dream long sought by patients and families. As our understanding of ferroptosis grows, so does the chance to design novel treatments that target this lethal form of cell death. Exploring the relationship between iron dysregulation, oxidative damage and neurodegeneration in HD may reshape our strategy for combating this tragic disease, offering up new pathways for revolutionary therapeutics.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"18 ","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversible posterior encephalopathy syndrome and metamizole: A new pharmacological precipitant?","authors":"André Aires Fernandes ,&nbsp;Fátima Hierro ,&nbsp;Frederico Garret ,&nbsp;Andreia Costa ,&nbsp;Carolina Soares","doi":"10.1016/j.dscb.2025.100204","DOIUrl":"10.1016/j.dscb.2025.100204","url":null,"abstract":"<div><h3>Introduction</h3><div>The link between reversible posterior encephalopathy syndrome (PRES) and certain drugs is well documented, especially for immunosuppressive and/or cytotoxic drugs. Metamizole is a non-opioid analgesic whose exact mechanism of action is still not fully understood, but it seems to involve the inhibition of prostaglandin synthesis. Prostaglandins are important vasoactive molecules involved in either arterial vasoconstriction and vasodilation, thus may promote loss of autoregulation of vascular circulation.</div></div><div><h3>Methods</h3><div>Description of a case of PRES after metamizole intake.</div></div><div><h3>Results</h3><div>An 18-year-old female with no significant medical history presented to the emergency department with new-onset generalized tonic-clonic seizures and visual disturbances. After reviewing the patient's medical records and brain MRI findings, the diagnosis of PRES was suspected, and classical precipitants were ruled out. However, the ingestion of metamizole was found to be the only plausible precipitating factor. The patient was treated with nimodipine 60 mg every 4 h and started on levetiracetam 500 mg twice daily. She was discharged asymptomatic and normotensive. The follow-up brain MRI performed three months after discharge was unremarkable.</div></div><div><h3>Conclusions</h3><div>This case-report may suggest a new pharmacological precipitant associated with PRES. Our hypothesis is that endothelial dysfunction resulting from the inhibition of the prostaglandin pathway may lead to the disruption of blood-brain barrier permeability, resulting in the loss of autoregulation of vascular circulation.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high cholesterol diet accelerates Alzheimer's progression by promoting fibrotic damage in rats","authors":"Ashmita Das ,&nbsp;Durlav Chowdhury ,&nbsp;Dilip Sharma ,&nbsp;Rahul Manna ,&nbsp;Surendra H. Bodakhe","doi":"10.1016/j.dscb.2025.100206","DOIUrl":"10.1016/j.dscb.2025.100206","url":null,"abstract":"<div><div>The literature documents the ability of oxysterols and TGFβ to cause fibrotic damage in the brain. Our study explores the potential mechanisms of oxysterol interactions with fibrotic mediators in Alzheimer's disease. It focuses on peripherally formed oxysterols and their effects on TGFβ hyperactivation in an experimental rodent model of Alzheimer's disease. We fed experimental rats a high-cholesterol diet for eight weeks and evaluated their cognitive abilities weekly using Hebb's Williams and Radial arm mazes. Using ELISA, we measured plasma and brain oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, claudin-5, and ATP Binding Cassette Transporter A1 expressions biweekly. The concentrations high density lipoprotein, low density lipoprotein, aspartate aminotransferase, and alanine transaminase were assessed using diagnostic kits, while the antioxidant profile was determined using UV spectroscopy. Our results indicated a synergistic increase in oxysterols, transforming growth factor β, amyloid β, matrix metalloproteinase-9, low density lipoprotein, aspartate aminotransferase, and alanine transaminase, with a concomitant decrease in the experimental animals' Claudin-5, ATP Binding Cassette Transporter A1, high density lipoprotein and antioxidant regulations. These findings suggest that a high-cholesterol diet may lead to oxysterol buildup, resulting in amyloid β accumulation due to transforming growth factor β hyperactivation. In conclusion, our study highlights the need to explore the role of oxysterols in the pathogenesis of Alzheimer's disease. By uncovering potential mechanisms underlying the interplay of oxysterols with fibrotic mediators, our study may pave the way for developing novel therapeutic approaches to manage Alzheimer's disease.</div></div>","PeriodicalId":72447,"journal":{"name":"Brain disorders (Amsterdam, Netherlands)","volume":"17 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}