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A systematic review of Phonological Components Analysis therapy studies for aphasia
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-26 DOI: 10.1016/j.brainresbull.2025.111269
Gregoire Python , Edith Durand , Michèle Masson-Trottier
{"title":"A systematic review of Phonological Components Analysis therapy studies for aphasia","authors":"Gregoire Python ,&nbsp;Edith Durand ,&nbsp;Michèle Masson-Trottier","doi":"10.1016/j.brainresbull.2025.111269","DOIUrl":"10.1016/j.brainresbull.2025.111269","url":null,"abstract":"<div><div>Among the wide range of anomia treatments for persons with aphasia (PWA), Phonological Components Analysis (PCA) is a well-known alternative. A systematic review of PCA efficacy studies for PWA was conducted to extract treatment-related and participant-related characteristics, to synthesise immediate and long-term outcomes and to assess the methodological quality of PCA studies (PROSPERO pre-registration CRD42024552047). Experimental studies on adults with post-stroke aphasia focusing on the efficacy of PCA published in English were included. Studies combining PCA with other treatment approaches, involving people with neurodegenerative disorders, without efficacy measures, or in dissertations, theses, and conference papers were excluded. The EBSCOhost platform and citations of the original PCA paper were last searched in November 2024. In total, thirteen studies were selected involving 89 PWA. Participants were at least 6 months post-stroke, and 75 % of them presented with Broca’s or anomic aphasia. The quality of PCA efficacy studies was relatively high according to the Single Case Experimental Design scale (mean 8.6 ± 1.0, range 7–10). Picture naming improved to reach at least a small effect size in 74 % of PWA (58/85) for trained items immediately after PCA and in 55 % of PWA (38/71) in the maintenance phase. Generalisation to untrained items occurred in 37 % of participants (22/59). Overall, PCA led to positive outcomes in the majority of PWA, which were often item-specific. As experimental designs were highly heterogeneous, further research is needed to better understand the optimal target population for PCA, the ideal dosage distribution, the key ingredients driving the improvement, and their neural correlates.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111269"},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522718","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}
引用次数: 0
Investigating mechanisms underlying the development of paralysis symptom in a model of MS
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-26 DOI: 10.1016/j.brainresbull.2025.111275
Shruti Gupta , Sreejita Arnab , Noah Silver-Beck , Kayla L. Nguyen , John R. Bethea
{"title":"Investigating mechanisms underlying the development of paralysis symptom in a model of MS","authors":"Shruti Gupta ,&nbsp;Sreejita Arnab ,&nbsp;Noah Silver-Beck ,&nbsp;Kayla L. Nguyen ,&nbsp;John R. Bethea","doi":"10.1016/j.brainresbull.2025.111275","DOIUrl":"10.1016/j.brainresbull.2025.111275","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder with approximately 80 % of patients suffering from pain and 50 % from paralysis. Using a rodent model for MS, experimental autoimmune encephalomyelitis (EAE), researchers have predominately investigated paralysis/motor disease as the clinical symptom of EAE with fewer studying MS/EAE pain. However, in EAE, all mice exhibit a pain like phenotype and only a subset progresses to paralysis. Despite extensive research characterizing the disease pathology, the etiology that contributes to the range of pain and motor symptom occurrence in MS remains understudied. This is the first study to dissect MS symptom pathophysiology, using the non-PTX EAE model, in mice that experience mechanical hypersensitivity (pain-like phenotype) with and without paralysis. We found that mechanical hypersensitivity experienced by mice with or without paralysis is comparable between the two groups, irrespective of sex. In addition, there is a significant increase in the activation and infiltration of immune cells, demyelination, and heightened protein expression of B cell chemoattractant CXCL13 within the spinal cord of mice exhibiting mechanical hypersensitivity and paralysis, compared to mice only experiencing mechanical hypersensitivity.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111275"},"PeriodicalIF":3.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143511044","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}
引用次数: 0
FMRI insights into the neural alterations and clinical correlates in multiple sclerosis: A comprehensive overview of systematic reviews and meta-analyses
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-25 DOI: 10.1016/j.brainresbull.2025.111278
Sama Rahnemayan , Arezoo Fathalizadeh , Mehdi Behroozi , Mahnaz Talebi , Amirreza Naseri , Elham Mehdizadehfar
{"title":"FMRI insights into the neural alterations and clinical correlates in multiple sclerosis: A comprehensive overview of systematic reviews and meta-analyses","authors":"Sama Rahnemayan ,&nbsp;Arezoo Fathalizadeh ,&nbsp;Mehdi Behroozi ,&nbsp;Mahnaz Talebi ,&nbsp;Amirreza Naseri ,&nbsp;Elham Mehdizadehfar","doi":"10.1016/j.brainresbull.2025.111278","DOIUrl":"10.1016/j.brainresbull.2025.111278","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammatory demyelination in the central nervous system. Functional Magnetic Resonance Imaging (fMRI) has emerged as an effective method for studying MS pathology. This review provides a comprehensive overview of fMRI applications, clarifying alterations in brain activity and identifying relevant biomarkers.</div></div><div><h3>Methods</h3><div>A systematic search of electronic databases and manual reference list checks at March 2024 yielded 470 articles. After duplicate removal, 456 articles underwent screening, 44 were assessed in full, and 12 systematic reviews and meta-analyses met inclusion criteria. Quality assessment was conducted.</div></div><div><h3>Results</h3><div>Included studies reported high methodological quality. fMRI revealed decreased functional connectivity within the default mode network, correlating with impaired information processing speed, and increased connectivity in compensatory networks during working memory tasks. Graph theory metrics identified disrupted global efficiency and clustering in functional networks, linked to gray matter atrophy. Neuroplasticity studies demonstrated cortical reorganization after cognitive rehabilitation, particularly in the prefrontal cortex. MS-related fatigue was associated with altered anterior cingulate cortex and thalamic activity, while depression correlated with reduced amygdala-prefrontal connectivity.</div></div><div><h3>Discussion</h3><div>fMRI has enhanced understanding of MS, revealing specific neural correlates of cognitive decline, neuroplasticity, fatigue, and depression. However, variability in MS subtypes and non-standardized protocols hinder consistency, while motion artifacts and cerebral blood flow changes complicate interpretation. Standardizing imaging protocols and integrating novel techniques could improve reliability and enable clinical applications to optimize patient monitoring and interventions.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111278"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522721","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}
引用次数: 0
Unveiling causal relationships between tobacco use phenotypes and neuroimaging: Insights from bidirectional Mendelian randomization and bibliometric analysis
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-25 DOI: 10.1016/j.brainresbull.2025.111277
ZhaoTao Zhang , LongTao Yang , HuaFang Guan , JiMan Shao , ZhiJian Chen , XinLan Xiao , XiaoYong Wu
{"title":"Unveiling causal relationships between tobacco use phenotypes and neuroimaging: Insights from bidirectional Mendelian randomization and bibliometric analysis","authors":"ZhaoTao Zhang ,&nbsp;LongTao Yang ,&nbsp;HuaFang Guan ,&nbsp;JiMan Shao ,&nbsp;ZhiJian Chen ,&nbsp;XinLan Xiao ,&nbsp;XiaoYong Wu","doi":"10.1016/j.brainresbull.2025.111277","DOIUrl":"10.1016/j.brainresbull.2025.111277","url":null,"abstract":"<div><div>Smoking is considered the most common addictive behavior worldwid. However, it is not systematically investigated whether there are bidirectional causal associations between tobacco use and neuroimaging, which might provide potential neural biomarkers or therapeutic neuro-targets for tobacco abuse or rehabilitation. In this study, using Mendelian randomization (MR), we explored both forward and reverse causal relationships between 4 tobacco use phenotypes (including Cigarettes per day, Smoking initiation, Age of initiation and Smoking cessation) and 209 neuroimaging features involving brain function and structure. Besides, we conducted a bibliometric analysis to find corresponding global trends of knowledge and specialized research areas. After Bonferroni correction, positive causal associations between cerebral global functional connectivity (FC) and smoking cessation, as well as between age of initiation and default mode network (DMN) structural connectivity (SC) were revealed; there were negative causal associations between mean diffusivity of left medial lemniscus and cigarette per day. Up to now, we also reveal that functional neuroimaging especially FC dominated smoking research field. Therefore, the discovery of causal relationships between smoking-related phenotypes and multi-modal cerebral alterations will promote a comprehensive understanding of tobacco addiction from cerebral function and structure perspective, facilitating the progression of personal treatment and risk prediction.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111277"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522727","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}
引用次数: 0
Treadmill exercise ameliorates hippocampal synaptic injury and recognition memory deficits by TREM2 in AD rat model
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-25 DOI: 10.1016/j.brainresbull.2025.111280
Linlin Zhang , Yanzhong Liu , Xin Wang , Hao Wu , Jiahui Xie , Yiping Liu
{"title":"Treadmill exercise ameliorates hippocampal synaptic injury and recognition memory deficits by TREM2 in AD rat model","authors":"Linlin Zhang ,&nbsp;Yanzhong Liu ,&nbsp;Xin Wang ,&nbsp;Hao Wu ,&nbsp;Jiahui Xie ,&nbsp;Yiping Liu","doi":"10.1016/j.brainresbull.2025.111280","DOIUrl":"10.1016/j.brainresbull.2025.111280","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;The impairment of cognitive function has been associated with Alzheimer’s disease (AD). Exercise exerts a positive modulatory effect on cognition by reducing synapse injury. However, limited in vivo evidence is available to validate the neuroprotective effect of TREM2 on synaptic function in this phenomenon. Here, we aim to explore whether physical exercise pretreatment alters Aβ-induced recognition memory impairment in structural synaptic plasticity within the hippocampus in AD rats.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods:&lt;/h3&gt;&lt;div&gt;In study 1, fifty-two Sprague-Dawley (SD) rats were randomly divided into following four groups: control group (C group, n = 13), Alzheimer’s disease group (AD group, n = 13), 4 weeks of physical exercise and Alzheimer’s disease group (Exe+AD group, n = 13), 4 weeks of physical exercise and blank group (Exercise group, n = 13). Four weeks of treadmill exercise intervention was performed, and AD model were established by intra-cerebroventricular injection (ICV) injection of Aβ&lt;sub&gt;1–42&lt;/sub&gt; protein. After 3 weeks, we also conducted a novel object test to evaluate recognition memory in the behavior assessment. Golgi staining and transmission electron microscopy were used to evaluate the morphology and synaptic ultrastructure of neurons. Western blotting was used to measure the expression of hippocampal synaptic proteins. Extracellular neurotransmitters in the hippocampus were detected by microdialysis coupled with high-performance liquid chromatography. In study 2, 33 SD rats were randomly divided into three groups: 4 weeks of physical exercise and Alzheimer’s disease group (Exe+AD group, n = 11), AAV-Control and physical exercise and Alzheimer’s disease group (AAV-Control+Exe+AD group, n = 11), AAV-TREM2 and physical exercise and Alzheimer’s disease group (AAV-TREM2 +Exe+AD group, n = 11). Stereotactic intracerebral injection in the bilateral hippocampus was performed to achieve microglial TREM2 down-expression by using adeno-associated virus (AAV) with CD68 promoter. After 4 weeks treadmill exercise and 3 weeks Aβ injection, all rats received behavior test and molecular experiment, which the same with experiment 2.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Novel recognition index in novel object recognition test significantly decreased, and western blot demonstrate that hippocampal TREM2 protein is significantly decreased (P &lt; 0.001). But physical exercise reversed this phenomenon(P &lt; 0.001). In addition, compared with Con group, the neuron from Exe+AD group exhibited a more complex branching pattern (P &lt; 0.05). And impaired synaptic ultrastructure was observed in AD group. Hippocampal synaptic-related protein (SYX, SYP, GAP43, PSD95) and neurotransmitter (DA, Glu, GABA) was also significantly decreased (P &lt; 0.01) in AD group. But the neuroprotection effect can be found in Exe+AD group, which are associated with the inhibition of synaptic injury by activate hippocampal TREM2 (P &lt; 0.05). How","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111280"},"PeriodicalIF":3.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522724","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}
引用次数: 0
A ketogenic diet decreases sevoflurane-induced burst suppression in rats
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-24 DOI: 10.1016/j.brainresbull.2025.111274
Morgan J. Siegmann , Samuel Parry , Arianna R.S. Lark , Fayaz A. Mir , Jinyoung Choi , Abigail Hardy Carpenter , Eliza A. Crowley , Christian G. White , Jiseung Kang , Patrick L. Purdon , Christa J. Nehs
{"title":"A ketogenic diet decreases sevoflurane-induced burst suppression in rats","authors":"Morgan J. Siegmann ,&nbsp;Samuel Parry ,&nbsp;Arianna R.S. Lark ,&nbsp;Fayaz A. Mir ,&nbsp;Jinyoung Choi ,&nbsp;Abigail Hardy Carpenter ,&nbsp;Eliza A. Crowley ,&nbsp;Christian G. White ,&nbsp;Jiseung Kang ,&nbsp;Patrick L. Purdon ,&nbsp;Christa J. Nehs","doi":"10.1016/j.brainresbull.2025.111274","DOIUrl":"10.1016/j.brainresbull.2025.111274","url":null,"abstract":"<div><h3>Background</h3><div>The brain requires a continuous fuel supply to support cognition and can get energy from glucose and ketones. Dysregulated brain metabolism is thought to contribute to perioperative neurocognitive disorders and anesthesia-induced burst suppression. Therefore, we investigated the relationship between brain metabolites and neurophysiology during the behavioral states of sleep and anesthesia under a standard diet (SD) or a ketogenic diet (KD).</div></div><div><h3>Methods</h3><div>We measured prefrontal cortex glucose, lactate, and electroencephalogram in Fischer344 rats during spontaneous sleep/wake followed by 3 % sevoflurane anesthesia. Nine rats were fed a KD and 8 rats a SD. To assess the role of adenosine receptor-mediated ketone activity on burst suppression, 5 additional rats on the KD received an intraperitoneal injection of vehicle or the adenosine A1 receptor antagonist, DPCPX, before 3 % sevoflurane.</div></div><div><h3>Results</h3><div>Sevoflurane induced larger fluctuations in glucose (p &lt; 0.001) and lactate (p = 0.015) concentrations compared to sleep as measured by the standard deviation (glucose 0.085 mM and lactate 0.16 mM in sleep/wake and 0.25 mM and 0.41 mM during sevoflurane respectively). Changes in glucose and lactate were closely tied to electrophysiological oscillations. Animals on the KD had reduced burst suppression ratio (mean 10 % in KD vs 30 % in SD) (p = 0.007) as well as increased time to loss of movement (mean 14 min in KD vs 8 min in SD) (p = 0.003) compared to SD. DPCPX in KD rats showed a trend to increased burst suppression, reduced the time to start of burst suppression (45 min in KD+vehicle to 37 min KD+DPCPX) (p = 0.007), and increased duration of burst suppression (49 min in KD+vehicle to 90 min in KD+DPCPX) (p = 0.046) compared to KD+vehicle.</div></div><div><h3>Conclusions</h3><div>It is thought that anesthesia-induced burst suppression reflects an underlying deficiency in brain energy. Accordingly, we found that upregulating ketones, which increase available brain ATP levels, delayed anesthetic induction and decreased burst suppression consistent with the idea that the underlying metabolic state of the brain influences an anesthetic’s effect on the brain. These findings suggest that metabolic interventions could be useful therapeutic targets to modulate brain activity during sleep and anesthesia. Future studies will examine whether ketones can reduce the cognitive symptoms associated with postoperative delirium.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111274"},"PeriodicalIF":3.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514799","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}
引用次数: 0
IL-2/anti-IL-2 complexes attenuates neuroinflammation and neurodegeneration in mice of experimental Parkinson's disease
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-23 DOI: 10.1016/j.brainresbull.2025.111273
Lanxin Li , Weiwei Gao , Ning Ren , Lei Chen
{"title":"IL-2/anti-IL-2 complexes attenuates neuroinflammation and neurodegeneration in mice of experimental Parkinson's disease","authors":"Lanxin Li ,&nbsp;Weiwei Gao ,&nbsp;Ning Ren ,&nbsp;Lei Chen","doi":"10.1016/j.brainresbull.2025.111273","DOIUrl":"10.1016/j.brainresbull.2025.111273","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is the second most common neurodegenerative disease, with motor and non-motor symptoms being its main clinical manifestations. Neuroinflammation has been shown to involve in pathogenesis of PD. Regulatory T cells (Tregs) in PD exhibited reduction in number and suppressive activity. Existing methods to increase the Tregs remains challenging for clinical application because of the difficulty in Tregs expanding or serious side-effects. Therefore, new approaches still need to be explored to balance the amount and activity of Tregs. In this study, we assessed the protective effects of IL-2/anti-IL-2 complexes (IL-2C) on mouse models of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). And the results showed that IL-2C significantly increased the number of Tregs both in spleen and brain, accompanied by reduced nigral dopaminergic neuron loss and behavioral defects. Besides, IL-2C also attenuated neuroinflammation as observed by diminished glial activation, fewer infiltration of CD4<sup>+</sup> and CD8<sup>+</sup> T cells and reduced pro-inflammatory cytokines releasing in the nigral region. Moreover, the protective effects of IL-2C were abolished by pre-treatment of anti-CD25 antibody (PC61), which was used to delete the Tregs. In summary, our results demonstrate that IL-2C-induced Tregs expansion attenuates the dopaminergic neurons loss and the neuroinflammatory response <em>in vivo</em>, suggesting that IL-2C maybe a promising therapeutic target for PD.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111273"},"PeriodicalIF":3.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499425","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}
引用次数: 0
Alpha-2 receptor mediates the endogenous antagonistic regulation of itch and pain via descending noradrenaline pathway from the locus coeruleus
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-23 DOI: 10.1016/j.brainresbull.2025.111270
Dan-Dan Hu , Wu Shi , Xin Jia , Fu-Ming Shao , Ling Zhang
{"title":"Alpha-2 receptor mediates the endogenous antagonistic regulation of itch and pain via descending noradrenaline pathway from the locus coeruleus","authors":"Dan-Dan Hu ,&nbsp;Wu Shi ,&nbsp;Xin Jia ,&nbsp;Fu-Ming Shao ,&nbsp;Ling Zhang","doi":"10.1016/j.brainresbull.2025.111270","DOIUrl":"10.1016/j.brainresbull.2025.111270","url":null,"abstract":"<div><div>Pain and itch are sensations that are regulated antagonistically; painful stimulation suppresses itch, while the inhibition of pain enhances itch. However, the central neural circuit underlying this antagonistic regulation remains elusive. The noradrenaline (NA) pathway from the locus coeruleus (LC) to the spinal cord (SC) constitutes an important component of endogenous descending pain inhibitory system. While the pathway of LC:SC has been extensively studied on pain modulation, its role in itch regulation remains poorly understood. We employed behavioral assays for itch and pain, immunofluorescence, electrophysiology, and chemogenetic techniques to investigate the role of noradrenergic (NAergic) neurons of LC (LC<sup>NA</sup> neurons)and their pathways in modulating itch and pain. Our study has demonstrated that LC<sup>NA</sup> neurons encode signals for both itch and pain. Inhibition of LC<sup>NA</sup> neurons had no effect on itch but enhanced pain behaviour. Surprisingly, inhibition of the NAergic projection of LC:SC increased pain and suppressed itch. Furthermore, intrathecal injection of an α2 adrenergic receptor antagonist, but not α1 or β receptor antagonists, produced effects similar to those observed when the LC:SC pathway was inhibited. Our research suggests that the descending NAergic pathway from LC to SC exerts endogenous antagonistic regulation on itch and pain through α2 receptors.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111270"},"PeriodicalIF":3.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499424","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}
引用次数: 0
Molecular dynamics study of stiffness and rupture of axonal membranes
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-22 DOI: 10.1016/j.brainresbull.2025.111266
Maryam Majdolhosseini , Svein Kleiven , Alessandra Villa
{"title":"Molecular dynamics study of stiffness and rupture of axonal membranes","authors":"Maryam Majdolhosseini ,&nbsp;Svein Kleiven ,&nbsp;Alessandra Villa","doi":"10.1016/j.brainresbull.2025.111266","DOIUrl":"10.1016/j.brainresbull.2025.111266","url":null,"abstract":"<div><div>Diffuse axonal injury (DAI), characterized by widespread damage to axons throughout the brain, represents one of the most devastating and difficult-to-treat forms of traumatic brain injury. Different theories exist about the mechanism of DAI, among which one hypothesis states that membrane poration of the axons initiates DAI. To investigate the hypothesis, molecular models of axonal membranes, incorporating 25 different lipids distributed asymmetrically in the leaflets, were developed using a coarse-grain description and simulated using molecular dynamics techniques. Different protein concentrations were embedded inside the lipid bilayer to describe the different sub-cellular parts in myelinated and unmyelinated axons. The models were investigated in equilibration and under deformation to characterize the structural and mechanical properties of the membranes, and comparisons were made with other subcellular parts, particularly myelin. Employing a bottom-top approach, the results were coupled with a finite element model representing the axon at the cell level. The results indicate that pore formation in the node-of-Ranvier occurs at a lower rupture strain compared to other axolemma parts, whereas myelin poration exhibits the highest rupture strains among the investigated models. The observed rupture strain for the node-of-Ranvier aligns with experimental studies, indicating a threshold for injury at axonal strains exceeding 10–13 % depending on the strain rate. The results indicate that the hypothesis suggesting mechanoporation triggers axonal injury cannot be dismissed, as this phenomenon occurs within the threshold of axonal injury.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"223 ","pages":"Article 111266"},"PeriodicalIF":3.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490745","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}
引用次数: 0
Biomechanical simulations of intracerebral hemorrhage expansion show tissue displacement has significant impact on electrical impedance tomography results
IF 3.5 3区 医学
Brain Research Bulletin Pub Date : 2025-02-22 DOI: 10.1016/j.brainresbull.2025.111265
Antti Paldanius , Jussi Toivanen , Nina Forss , Daniel Strbian , Ville Kolehmainen , Jari Hyttinen
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