Journal of Neuroscience Methods最新文献

{"title":"Generation of stable brain cell cultures from embryonic zebrafish to interrogate phenotypes in zebrafish mutants of neurodevelopmental disorders","authors":"G. Lorenzo Odierna ,&nbsp;Sarah Stednitz ,&nbsp;April Pruitt ,&nbsp;Joshua Arnold ,&nbsp;Ellen J. Hoffman ,&nbsp;Ethan K. Scott","doi":"10.1016/j.jneumeth.2025.110426","DOIUrl":"10.1016/j.jneumeth.2025.110426","url":null,"abstract":"<div><h3>Background</h3><div>Zebrafish are a popular model system to study the genetic and neural basis of perception and behavior. Cultured primary neurons provide a complementary tool for such studies, but existing protocols for culturing embryonic zebrafish neurons are limited by short cell survival and low neuronal purity. In this study, we set out to establish a protocol to produce long lived brain cell cultures from zebrafish that could be used to study the mechanistic contributions of genes to neuronal networks.</div></div><div><h3>New method</h3><div>This protocol improves the viability of embryonic zebrafish primary brain cell cultures. We successfully optimized several parameters to generate long lived mixed cell type or pure neuronal cultures derived from embryonic zebrafish.</div></div><div><h3>Results</h3><div>Our optimized protocol produces cultures that form stable networks of neurons expressing the structural hallmarks of mature synaptic connections. As proof of principle, we apply our protocol to explore the cellular consequences of <em>scn1lab</em> loss of function. We find that loss of <em>scn1lab</em> results in increased prevalence of non-neuronal cells consistent with transcriptional signatures from embryonic tissue, providing support for the utility of our protocol.</div></div><div><h3>Comparison with existing method(s)</h3><div>Most existing embryonic zebrafish primary neuron culture protocols describe growing mixed cell types for short durations, with a reported maximum of 9 days <em>in vitro</em>. Here, we describe a protocol that produces cultures viable for over 100 days.</div></div><div><h3>Conclusions</h3><div>The protocol reported in this study raises embryonic zebrafish primary brain cell culture to similar standards observed by well-established methods using cell lines or mammalian tissue.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110426"},"PeriodicalIF":2.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishing the electrophysiological feasibility of the rabbit median nerve as an experimental model for carpal tunnel syndrome","authors":"Semra Çınar ,&nbsp;Erkut Turan ,&nbsp;Ayşe Nur Akkoç","doi":"10.1016/j.jneumeth.2025.110411","DOIUrl":"10.1016/j.jneumeth.2025.110411","url":null,"abstract":"<div><h3>Backround</h3><div>Rabbits are appropriate models for experimental carpal tunnel syndrome (CTS) studies. This study aimed to explore whether the distribution and innervation area of the nerves supplying the thenar muscles of rabbits are similar to those in humans using anatomical, electrophysiological, and histopathological methods.</div></div><div><h3>New method</h3><div>20 New Zealand rabbits were used to establish reference conduction values for the median and ulnar nerves. Median nerve denervation was performed on the left forelimb of six rabbits, and changes were assessed 33 days post-surgery. Normative data from healthy rabbits were compared with those from denervated rabbits, and comparisons were made between the right and left forelimbs of the denervated rabbits. Thenar and interosseous (2nd, 3rd, and 4th) muscles were used for histopathology. Dissections focused on the thenar muscles and branches of the median and ulnar nerves.</div></div><div><h3>Results</h3><div>Thenar muscles were 2.5–3 mm in width and 7–8 mm in length), innervated by both the median and ulnar nerves. Normative latency and amplitude values of 1.85 ± 0.30 ms and 7.71 ± 3.50 mV for the median nerve and 1.85 ± 0.19 ms and 6.14 ± 2.50 mV for the ulnar nerve, respectively. Denervation reduced thenar muscle CMAP amplitude (2.51 ± 2.16 mV, p = 0.047) on ulnar nerve stimulation, indicating dual innervation. The median sensory nerve conduction latency (2.55 ± 0.20 ms) was successfully performed for the first time. Histopathological analysis revealed localized atrophy and degenerative changes in the denervated thenar muscles.</div></div><div><h3>Comparison with existing methods</h3><div>The new method including novel normative data will significantly enhance the evaluation of CTS in experimental rabbit models, paving the way for more accurate and reliable future research.</div></div><div><h3>Conclusion</h3><div>The innervation patterns of rabbit thenar muscles were similar to those in humans. This data can aid CTS understanding in rabbit models.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110411"},"PeriodicalIF":2.7,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing therapeutic efficacy of fingolimod via intranasal delivery in an ethidium bromide-induced model of multiple sclerosis","authors":"Anshul Sharma ,&nbsp;Nitin Sharma ,&nbsp;Kushagra Khanna ,&nbsp;Akshita Arora ,&nbsp;Sidharth Mehan ,&nbsp;Anjana Sharma","doi":"10.1016/j.jneumeth.2025.110415","DOIUrl":"10.1016/j.jneumeth.2025.110415","url":null,"abstract":"<div><h3>Background</h3><div>Multiple sclerosis (MS) is a chronic inflammatory autoimmune neurological characterized by muscle weakness, numbness, tingling, vision problems, and difficulty in coordination and balance caused by the damage of myelin content around the nerve fibres. The recent literature is evident that along with their lymphocyte attack prevention mechanism, fingolimod (FNG) can serve as neuroprotective also by ensuring their improved brain availability. Therefore, in this project brain availability of FNG was enhanced by delivering the FNG in the form of nanoparticles.</div></div><div><h3>New methods</h3><div>Fingolimod-loaded solid lipid nanoparticles (FNG-SLNs) were prepared using the solvent evaporation method and formulation factors (lipid concentration; X1, speed; X2, surfactant concentration; X3) and response were established by factorial design. FNG-SLNs were characterized for particle size, entrapment efficiency and i<em>n-vitro</em> drug release. Optimized formulations were characterized for <em>in-vivo</em> efficacy study in ethidium bromide-induced MS rat model.</div></div><div><h3>Result</h3><div>Obtained data revealed that the particle size and entrapment efficiency of FNG-SLNs optimized formulation was 125.4 nm and 79.86 % w/w respectively. <em>In-vitro</em> drug release study showed an initial burst release of the FNG up to 32.52 % in 30 min followed by sustained drug release up to 78.22 % in 24 h. Furthermore, <em>in-vivo</em> data of FNG-SLNs on ethidium bromide-induced MS rat model revealed better treatment response by showing several evidence such as signs of remyelination, restoration of neuron shape, and the recovered oligodendrocytes.</div></div><div><h3>Comparison with existing methods</h3><div>To the best of our knowledge this article demonstrates improved efficacy of FNG using SLNs.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the successful development of FNG-SLNs to enhance the therapeutic efficacy of FNG for the treatment of multiple sclerosis.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110415"},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-view graph fusion of self-weighted EEG feature representations for speech imagery decoding","authors":"Zhenye Zhao ,&nbsp;Yibing Li ,&nbsp;Yong Peng ,&nbsp;Kenneth Camilleri ,&nbsp;Wanzeng Kong","doi":"10.1016/j.jneumeth.2025.110413","DOIUrl":"10.1016/j.jneumeth.2025.110413","url":null,"abstract":"<div><h3>Background:</h3><div>Electroencephalogram (EEG)-based speech imagery is an emerging brain–computer interface paradigm, which enables the speech disabled to naturally and intuitively communicate with external devices or other people. Currently, speech imagery research decoding performance is limited. One of the reasons is that there is still no consensus on which domain features are more discriminative.</div></div><div><h3>New method:</h3><div>To adaptively capture the complementary information from different domain features, we treat each domain as a view and propose a multi-view graph fusion of self-weighted EEG feature representations (MVGSF) model by learning a consensus graph from multi-view EEG features, based on which the imagery intentions can be effectively decoded. Considering that different EEG features in each view have different discriminative abilities, the view-dependent feature importance exploration strategy is incorporated in MVGSF.</div></div><div><h3>Results:</h3><div>(1) MVGSF exhibits outstanding performance on two public speech imagery datasets (2) The learned consensus graph from multi-view features effectively characterizes the relationships of EEG samples in a progressive manner. (3) Some task-related insights are explored including the feature importance-based identification of critical EEG channels and frequency bands in speech imagery decoding.</div></div><div><h3>Comparison with existing methods:</h3><div>We compared MVGSF with single-view counterparts, other multi-view models, and state-of-the-art models. MVGSF achieved the highest accuracy, with average accuracies of 78.93% on the 2020IBCIC3 dataset and 53.85% on the KaraOne dataset.</div></div><div><h3>Conclusions:</h3><div>MVGSF effectively integrates features from multiple domains to enhance decoding capabilities. Furthermore, through the learned feature importance, MVGSF has made certain contributions to identify the EEG spatial-frequency patterns in speech imagery decoding.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110413"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direction of TIS envelope electric field: Perpendicular to the longitudinal axis of the hippocampus","authors":"Weiyu Meng ,&nbsp;Cheng Zhang ,&nbsp;Changzhe Wu ,&nbsp;Xiaolin Huo ,&nbsp;Guanghao Zhang","doi":"10.1016/j.jneumeth.2025.110416","DOIUrl":"10.1016/j.jneumeth.2025.110416","url":null,"abstract":"<div><h3>Background</h3><div>Temporal Interference Stimulation (TIS) is a non-invasive approach to deep brain stimulation. However, most research has focused on the intensity of modulation, with limited attention given to the directional properties of the induced electric fields, despite their potential importance for precise stimulation.</div></div><div><h3>New methods</h3><div>A novel analytical framework was developed to analyze TIS-induced electric field directions using individual imaging data. For each voxel, the direction corresponding to the maximal modulation depth was calculated. The consistency of these directions within regions of interest (ROIs) and their alignment with the ROI principal axes, derived from principal component analysis (PCA), were assessed.</div></div><div><h3>Results</h3><div>Simulations revealed complex spatial and temporal trajectories of the electric field at the voxel level. In the left putamen, the maximal modulation depth reached 0.241 ± 0.041 V/m, whereas in the target region, the left hippocampus, it was lower (0.15 ± 0.032 V/m). Notably, in the left hippocampus, the directions of maximal modulation depth were predominantly perpendicular to its longitudinal axis (84.547 ± 8.776°), reflecting structural specificity across its anterior, middle, and posterior regions.</div></div><div><h3>Comparison with existing methods</h3><div>Unlike previous approaches, this study integrates directional analysis into TIS modeling, providing a foundation for precise stimulation by exploring structural alignment.</div></div><div><h3>Conclusion</h3><div>Our analysis revealed that the orientations of maximal modulation depth in the left hippocampus were perpendicular to its longitudinal axis under the current electrode configuration, but they shifted to parallel alignment when the electrode pairs were swapped. This directional specificity offers insights for optimizing TIS by aligning with structural features, presenting a potential strategy to enhance stimulation precision and broaden its clinical and research applications.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110416"},"PeriodicalIF":2.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the efficacy of non-invasive brain stimulation techniques in managing pediatric epilepsy","authors":"Guangshun Hou,&nbsp;Yujie Guo,&nbsp;Chuanmei Chen,&nbsp;Xinghua Cui,&nbsp;Zaifen Gao,&nbsp;Fang Qi","doi":"10.1016/j.jneumeth.2025.110412","DOIUrl":"10.1016/j.jneumeth.2025.110412","url":null,"abstract":"<div><h3>Background</h3><div>Pediatric epilepsy significantly affects cognitive and developmental outcomes, with drug-resistant epilepsy (DRE) posing a major challenge. While pharmacological and surgical interventions remain standard treatments, they often fail in refractory cases. Non-Invasive Brain Stimulation (NIBS), including Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS), has emerged as a promising therapeutic alternative.</div></div><div><h3>New method</h3><div>This study systematically reviews and compares the efficacy, safety, and feasibility of TMS and tDCS in pediatric epilepsy. The analysis evaluates seizure reduction, cognitive improvements, and treatment tolerability. A comparative assessment considers mechanisms of action, precision, accessibility, and clinical applications.</div></div><div><h3>Results</h3><div>TMS and tDCS treatments produce a 30–40 % seizure reduction effect in addition to attaining enhanced attention and memory functions. TMS provides top-level spatial precision but tDCS allows low-cost portable treatment that suits home use. Studies show that patients experience minimal and short-term discomfort on their scalp but only minor headaches as reported side effects.</div></div><div><h3>Comparison with existing methods</h3><div>Compared to pharmacological treatments, NIBS offers a non-invasive alternative with fewer systemic side effects. Unlike surgery, which requires invasive intervention, NIBS is safe, repeatable, and adaptable. However, cost (TMS), lack of standardization, and patient response variability remain challenges to clinical adoption.</div></div><div><h3>Conclusions</h3><div>NIBS is a safe and effective alternative for pediatric epilepsy but requires protocol standardization, accessibility improvements, and long-term efficacy validation. Future research should focus on biomarker-driven personalized treatments, AI-optimized stimulation, and affordable device development for broader clinical applications.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110412"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An immunohistochemical protocol for visualizing adrenergic receptor subtypes in the rhesus macaque hippocampus","authors":"Kelsey E. McDermott ,&nbsp;Carol A. Barnes","doi":"10.1016/j.jneumeth.2025.110410","DOIUrl":"10.1016/j.jneumeth.2025.110410","url":null,"abstract":"<div><h3>Background</h3><div>The noradrenergic system is an important modulatory system in the brain, and dysfunction in this system is implicated in multiple neurodegenerative diseases. The study of this system in neuronal tissues relies on the availability of specific antibodies but to date no protocol exists for immunohistological visualization of α1, α2, and β adrenergic receptors in rhesus macaques.</div></div><div><h3>New method</h3><div>Here, we test the ability of various commercially available antibodies to detect these receptors in the primate brain and develop a protocol for visualization of receptors alongside noradrenergic axons and glial and vascular cells that interact with the noradrenergic system.</div></div><div><h3>Results</h3><div>Of the eleven primary antibodies for adrenergic receptors tested, five did not produce staining at any concentration. The remaining six antibodies underwent a preadsorption protocol to determine specificity of the antibody to its’ immunogen sequence. Two antibodies failed this test, indicating they were binding to other targets in the brain. We then determined optimum concentrations for the remaining four antibodies. Additionally, we develop an immunofluorescence protocol that allows for the visualization of each AR - α1, α2a, or β1 – along with adrenergic axons as well as with glia and vasculature.</div></div><div><h3>Comparison with existing methods</h3><div>While protocols exist for visualizing receptors in rodents, this is the first protocol for use in nonhuman primates.</div></div><div><h3>Conclusions</h3><div>Seven out of the eleven tested antibodies were inaccurate, highlighting the importance of comprehensive testing. The stringent tests conducted here suggest that some commercially available antibodies can reliably detect adrenergic receptor subtypes in nonhuman primate tissue.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110410"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 3D Vertical Maze: A new model system for studying the interactions between social and spatial cognition","authors":"Taylor B. Wise ,&nbsp;Victoria L. Templer ,&nbsp;Rebecca D. Burwell","doi":"10.1016/j.jneumeth.2025.110414","DOIUrl":"10.1016/j.jneumeth.2025.110414","url":null,"abstract":"<div><h3>Background</h3><div>Evolutionary biology and neuroscience evidence supports the theory that spatial cognition and social cognition share neural mechanisms. Although rodent models are widely used to study either spatial or social cognition, few studies have explored the interactions between these domains, possibly because measures across tasks differ.</div></div><div><h3>New method</h3><div>We introduce the automated 3-dimensional Vertical Maze (VM), a new model system designed to measure multiple aspects of spatial and social behavior and cognition. The VM features a standard 3-chamber maze positioned above three-level columns allowing for presentation of conspecifics as either demonstrators or discriminative stimuli at different spatial distances and different social familiarity levels. The presentation of demonstrators below the perforated floors of the 3-chamber level encourages rats to use multisensory cues to judge distance, direction, and social identity of conspecifics.</div></div><div><h3>Results</h3><div>Using the VM, we found that rats showed normal social preferences whether demonstrators were presented at the near, middle, or far distance. In an operant spatial distance discrimination task, rats readily learned to associate a reward with the spatial distance of a demonstrator.</div></div><div><h3>Comparison with existing methods</h3><div>This new paradigm advances the field by permitting the presentation of social information (conspecifics) at different spatial distances allowing more direct comparison of behavioral measures across social and spatial information domains.</div></div><div><h3>Conclusions</h3><div>The VM is an effective tool for studying both spatial and social cognition opening new avenues for investigating the neural and cognitive foundations of spatial and social behavior and for exploring the possibility of shared mechanisms across these cognitive domains.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110414"},"PeriodicalIF":2.7,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 3D-printed modular implant for extracellular recordings","authors":"Dorian Röders ,&nbsp;Jesus J. Ballesteros ,&nbsp;Celil Semih Sevincik ,&nbsp;Sara Santos Silva ,&nbsp;Luca Bürgel ,&nbsp;Bilal Abbas ,&nbsp;Yannik Neukirch ,&nbsp;Roland Pusch ,&nbsp;Jonas Rose","doi":"10.1016/j.jneumeth.2025.110407","DOIUrl":"10.1016/j.jneumeth.2025.110407","url":null,"abstract":"<div><h3>Background</h3><div>Chronic implants for neural data acquisition must meet several criteria that can be difficult to integrate. Surgical procedures should be as short as possible to reduce unnecessary stress and risks, yet implants must precisely fit to the location of interest and last long periods of time. Implants also must be lightweight but stable enough to withstand the subject’s daily life and experimental needs.</div></div><div><h3>New method</h3><div>Here we introduce a novel, 3D-printed and open-source modular implant. Our modular design philosophy allows altering parts of the implant either before implantation or later, during the course of experiments. The implant consists of a base individually designed, for instance using an MRI of the subject for an exact skull fit. This base remains permanently on the subject and can contain multiple sites for craniotomies, microdrives and head stage connectors. All movable components (drives with probes, connectors, reference/ground points) are securely screwed onto this base, allowing for replacement and recovery.</div></div><div><h3>Results</h3><div>After implantation of the bases, self-made microdrives carrying commercial silicon probes were implanted. Once the experimental goals were achieved, they were recovered for further use. Should the quality of the data decrease during the experimental period, the components were replaced, allowing for the experimentation to continue. On an exemplary free-moving subject, under wireless electrophysiological data collection, we reliably obtained single and multi unit data up to 86 days after a silicon probe implantation. In this specific case, after this time we successfully substituted the components and collected similar quality data for additional 11 days.</div></div><div><h3>Comparison with existing methods</h3><div>Our approach allows to remove, reposition and exchange components during minimally invasive procedures, not requiring new incisions, bone drilling (unless new craniotomies are planned sequentially) or removal of dental cement or glue structures. Splitting complex implantations into multiple shorter procedures reduce the risks inherent to long surgical procedures. A careful plan of action allows to re-use and reduce subject's usage.</div></div><div><h3>Conclusion</h3><div>This novel approach reduces the duration of surgical procedures. It allows for minimally invasive follow-up procedures, including component replacements between experiments. The design is stable, proven to yield good results, in a very long-term period. This approach increases the chance of successful long experimental paradigms, and help reducing the use of subjects.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110407"},"PeriodicalIF":2.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A large animal model for focal stroke: Photothrombotic lesion in the cortex of Danish Landrace pigs","authors":"V.H. Kuang ,&nbsp;C.S. Skoven ,&nbsp;S. Arvin ,&nbsp;L.M. Fitting ,&nbsp;K.R. Drasbek ,&nbsp;B. Hansen ,&nbsp;D. Orlowski ,&nbsp;J.C.H. Sørensen","doi":"10.1016/j.jneumeth.2025.110408","DOIUrl":"10.1016/j.jneumeth.2025.110408","url":null,"abstract":"<div><h3>Background</h3><div>Preclinical rodent models have been crucial for studying stroke pathophysiology. However, the limited success of translating these ischemic stroke models to human trials highlights their shortcomings. To address this, we developed a large animal porcine stroke model using Rose Bengal (RB) for photothrombotic ischemic lesioning.</div></div><div><h3>New method</h3><div>Four Danish Landrace pigs (4–6 months old, 36–40 kg) were used in this proof-of-concept study. RB (20 mg/kg) was infused via a central venous catheter, and lesion sites in the motor and visual cortices were targeted using MRI, a stereotactic frame, and fiducial markers. Surgical access was achieved through burr holes, followed by green light exposure through the dura onto the neocortex for 30 mins. After recovery, the pigs underwent motor behavior assessment, euthanasia, and histological and MRI analyses.</div></div><div><h3>Results</h3><div>Post-stroke, significant motor deficits were observed. Three pigs were hemiparetic and immobile, while one showed reduced exploratory behavior (42 % post-stroke vs. 81 % pre-stroke) and peripheral sniffing (∼0 % vs. 9 %). Histological analysis revealed ischemic changes, including nuclear shrinkage, pyknosis, and infarct zones with blood clots. Lesion size ranged from 1 mm² to 18 mm². Ex vivo diffusion MRI showed increased mean kurtosis in three pigs, confirming microstructural changes.</div></div><div><h3>Comparison with existing methods and conclusions</h3><div>The model produced behavioral and histological characteristics in pigs, which have gyrencephalic brains, large intracranial vessel diameters, and a high white-to-gray matter ratio, similar to those observed in other animals and traditional models. This model can produce a reproducible isolated cortical lesion using stereotactic coordinates and/or 3D imaging.</div></div>","PeriodicalId":16415,"journal":{"name":"Journal of Neuroscience Methods","volume":"418 ","pages":"Article 110408"},"PeriodicalIF":2.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}