Journal of Neuroscience Research最新文献

{"title":"Neonatal Freeze Lesion-Induced Cortical Malformation Alters Hippocampal Gene Expression and Leads to Persistent Cognitive and Emotional Deficits in Adult Male Wistar Rats","authors":"Olga E. Zubareva,&nbsp;Anna A. Kovalenko,&nbsp;Denis S. Sinyak,&nbsp;Tatyana Y. Postnikova,&nbsp;Marat R. Subkhankulov,&nbsp;Elmira R. Sabirova,&nbsp;Aleksey V. Zaitsev","doi":"10.1002/jnr.70077","DOIUrl":"https://doi.org/10.1002/jnr.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Cortical malformations, including microgyria, are often associated with neurodevelopmental comorbidities such as epilepsy and cognitive impairments in humans. To investigate how early cortical disruption leads to persistent behavioral impairments, we employed a neonatal neocortical focal freeze lesion (FFL) model of polymicrogyria in male Wistar rats. Unilateral cortical lesions were induced at postnatal day 0 (P0), and molecular changes in hippocampal gene expression (glutamatergic signaling: <i>Grin1</i>, <i>Grin2a</i>, <i>Grin2b</i>, <i>Gria1</i>, <i>Gria2</i>; neuroinflammation: <i>Nlrp3</i>, <i>Il1b</i>, <i>Il1rn</i>; glial markers: <i>Gfap</i>, <i>Aif1</i>; neurotrophic factors: <i>Bdnf</i>, <i>Fgf2</i>) were analyzed at P21. Behavioral outcomes, including locomotor activity, exploratory behavior, anxiety-like behavior, social interaction, and recognition memory, were assessed in adulthood (P70–P90). Neonatal cortical lesions induced subregion-specific alterations in hippocampal gene expression: <i>Grin2b</i> and <i>Gria1</i> expression decreased in the ipsilateral dorsal hippocampus, while <i>Grin2a</i>, <i>Bdnf</i>, and <i>Fgf2</i> increased in the contralateral ventral hippocampus. These molecular changes were associated with subsequent cognitive deficits (impaired recognition memory) and emotional dysregulation (heightened anxiety-like behavior) in adult rats, alongside reduced exploratory activity. Basic motor functions and sociability remained unaffected, and seizure susceptibility (assessed via maximal electroshock threshold) was unchanged, highlighting the specificity of the observed impairments. Our findings suggest a potential mechanistic link between early-life cortical malformations with microgyrus formation, dysregulation of hippocampal synaptic plasticity and neurotrophic signaling, and persistent neurobehavioral deficits. These results underscore the translational relevance of the freeze lesion model for studying the neurodevelopmental trajectory of cortical malformation-related comorbidities.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910389","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":"Investigating Atypical Neural Dynamics and Gene Expression in Temporal Lobe Epilepsy: Insights From Co-Activation Patterns","authors":"Lu Qin,&nbsp;Bailing Qin,&nbsp;Liya Pan,&nbsp;Qin Zhou,&nbsp;Huoyou Hu,&nbsp;Shujun Su,&nbsp;Yuting Sun,&nbsp;Xiaomin Pang,&nbsp;Zirong Chen,&nbsp;Jinou Zheng","doi":"10.1002/jnr.70076","DOIUrl":"https://doi.org/10.1002/jnr.70076","url":null,"abstract":"<div>\u0000 \u0000 <p>Temporal lobe epilepsy (TLE) is a focal epilepsy extensively examined through advanced neuroimaging techniques to elucidate its pathophysiological mechanisms. This study investigates the differences in dynamic brain activity and gene expression in TLE patients. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 60 TLE patients and 30 healthy controls (HC). Dynamic amplitude of low-frequency fluctuations (dALFF) was employed to identify regions with dALFF variance differences, which were then designated as regions of interest (ROIs). Co-activation patterns (CAP) was constructed to compare brain dynamic changes. Pearson's correlation analysis and pathway enrichment analysis were used to explore the potential molecular mechanisms associated with atypical neural dynamics in TLE. Five CAP states were identified from the rs-fMRI data. Compared to HC, TLE with cognitive normal (TLE-CN) and TLE with cognitive impairment (TLE-CI) patients exhibited atypical state-specific temporal characteristics, including number of states (counts), fraction of time, persistence, resilience, and transition probability (TP) between states. Importantly, dynamic indicators of CAP states were significantly correlated with cognitive performance. Furthermore, 2752 genes were significantly associated with atypical dynamic brain states in TLE, with these genes primarily enriched in synapse-related pathways. This study offers novel insights into atypical neural dynamics from a temporal perspective. The brain network dynamics defined by CAP analysis deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, revealing a link between atypical neural architecture and gene expression in TLE.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144909929","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":"Effects of Small Conductance Ca2+-Activated Potassium Channel Agonists on SLEs in Varied Epilepsy Models, From Animal Slices to Pharmacoresistant Human Tissue","authors":"Muhammad Liaquat Raza,&nbsp;Rizwan-Ul Haq,&nbsp;Uwe Heinemann","doi":"10.1002/jnr.70078","DOIUrl":"https://doi.org/10.1002/jnr.70078","url":null,"abstract":"<div>\u0000 \u0000 <p>To assess the impact of SK channel agonists on seizure-like events (SLEs) in various seizure models in slices of the temporal cortex obtained from pharmacoresistant patients. SLEs were triggered by applying 4-aminopyridine (100 μM) to slices of the entorhinal cortex taken from both normal and pilocarpine-treated rats. Additionally, SLEs were induced in slices of the temporal cortex obtained from individuals who had undergone epilepsy surgery. In the case of human slices, SLEs were also provoked by increasing potassium levels along with the administration of either 4-AP (100 μM) or bicuculline (50 μM). The activation of SK2/3 channels by the compound CYPPA (<i>n</i> = 8) effectively prevented SLEs in slices from the brains of normal rats, pilocarpine-treated rats (<i>n</i> = 8), and in human cortex slices (<i>n</i> = 9) when SLEs were triggered by 4-AP. In human temporal cortex slices, CYPPA also demonstrated efficacy in preventing SLEs induced by an elevation in potassium concentration combined with bicuculline application (<i>n</i> = 5). SKA-31, exhibited efficacy in slices from normal rats (<i>n</i> = 8), rats treated with pilocarpine (<i>n</i> = 8), and in human slices (<i>n</i> = 7) when SLEs were provoked by 4-AP. However, its effectiveness was limited when applied to human tissue slices exposed to bicuculline and elevated potassium levels. The SK1 channel activator GW-542573X displayed only moderate anticonvulsant effects in the models under investigation. SK2 channels showed the highest effectiveness across the different epilepsy models. Sensitivity to the SK3 channel activator was found to be more pronounced compared to the other two activators studied.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144909928","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":"Enoxaparin Improves Outcomes in Cerebral Infarction Rats by Reducing Microcirculatory Thrombosis and Hypoperfusion","authors":"Yao Li,&nbsp;Ding'an Zheng,&nbsp;Liuliu Xiong,&nbsp;Jingye Wang","doi":"10.1002/jnr.70075","DOIUrl":"https://doi.org/10.1002/jnr.70075","url":null,"abstract":"<div>\u0000 \u0000 <p>Microcirculatory disturbances may play an important role in futile recanalization. This study investigated the early factors affecting the prognosis of cerebral infarction in rats and whether low-molecular-weight heparin improves microcirculation disorders. We used a male rat middle cerebral artery occlusion (MCAO) model with 90 min transient MCAO (tMCAO) or permanent MCAO (pMCAO) ischemia, and analyzed after 24 h. Cortical blood flow was monitored using laser speckle blood flow imaging. Furthermore, 1.5 mg/kg Enoxaparin (Enox) was administered 30 min before ischemia or 1 h post-reperfusion. The tMCAO group received saline. Our results showed that the proportion of moderate and severe (M&amp;S) injuries was 54.2% in tMCAO rats, 100% in pMCAO rats, and reduced to 25% in the enoxaparin pre-ischemic (Enox-pre) group. The reperfusion rats had persistent hypoperfusion and the lowest blood flow after 1 h post-reperfusion. The 1 and 24 h post-reperfusion cortical blood flow was negatively correlated with infarct volume and neurological scores. The Enox-pre group had higher blood flow than the tMCAO group at 1 h post-reperfusion (<i>p</i> &lt; 0.05). Enox-pre reduced fibrin deposition after 1 h post-reperfusion (<i>p</i> &lt; 0.01), improved microvascular patency after 1 and 24 h (<i>p</i> &lt; 0.01), and decreased Evans blue leakage after 24 h (<i>p</i> &lt; 0.001). We concluded that 50% of the futile recanalization rate also exists in rats with recanalization 1.5 h post-infarction. The degree of reperfusion blood flow recovery significantly affects cerebral infarction outcomes. Enox-pre reduces the proportion of poor outcomes by reducing early microthrombus formation, enhancing microcirculation, increasing reperfusion blood flow, and mitigating blood–brain barrier (BBB) disruption.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144811152","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 Ketogenic Diet Consumption on the Sporadic Alzheimer's Model Through MT1/MT2 Regulation","authors":"Yasin Ali Cimen,&nbsp;Birsen Elibol,&nbsp;Nur Damla Korkmaz,&nbsp;Mazlum Yuzgulec,&nbsp;Beyza Kinsiz,&nbsp;Selim Kutlu,&nbsp;Savas Ustunova","doi":"10.1002/jnr.70070","DOIUrl":"https://doi.org/10.1002/jnr.70070","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin and its receptors play a primary role in regulating circadian rhythms, which are frequently disrupted in patients with Alzheimer's disease (AD). Furthermore, there is increasing evidence that the use of a ketogenic diet (KD) delays the onset of AD. Therefore, we aimed to investigate whether KD has an ameliorative effect on AD through the regulation of melatonin receptors. In this study, male Sprague–Dawley rats were divided into three groups: sham, AD, and KD. At the end of KD supplementation, behavioral parameters were determined by the Morris Water Maze. Melatonin levels, protein expression levels, and immunoreactivity of MT1–MT2 in thehippocampus and striatum were determined by ELISA, Western blotting, and immunofluorescence staining, respectively. As a result, KD improved memory decline in AD rats. Also, KD increased melatonin levels in the hippocampus but did not affect striatum melatonin levels. MT1 expression tended to increase in the hippocampus of the AD group, while MT2 expression decreased. On the contrary, KD treatment increased both MT1 and MT2 expressions. In the striatum, there was no change in MT1 expression in the AD and KD groups, but MT2 expression increased in the AD group compared with the sham group and was suppressed in the KD group. In addition, KD treatment reduced streptozotocin-induced apoptosis and neuroinflammation in the hippocampus and striatum. Our results suggest that KD may improve AD-associated inflammation and apoptosis by altering melatonin levels and the expression of MT2 receptors in the hippocampus and striatum. Therefore, KD may be a promising preventive and therapeutic option for AD.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758600","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":"PPP1R15A Promotes Apoptosis, Autophagy, and Inflammatory Response to Exacerbate Ischemic Stroke Through Activation of TLR4/NF-κB Pathway","authors":"Lijuan Liu,&nbsp;Jian Li,&nbsp;Ping Yin,&nbsp;Shuangyan Kong,&nbsp;Jingxin Li","doi":"10.1002/jnr.70073","DOIUrl":"https://doi.org/10.1002/jnr.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemic stroke (IS) is a prevalent and serious neurological disorder, and is one of the major contributors to mortality and disability worldwide. The activation of autophagy and the inflammatory response following cerebral ischemia are crucial in the progression of IS. Protein phosphatase 1 regulatory subunit 15A (PPP1R15A), as a stress-responsive protein, has been proven to be closely associated with autophagy. Nevertheless, the molecular mechanism of PPP1R15A in IS remains to be fully understood. Our study screened PPP1R15A as a candidate gene by bioinformatics analysis of the differentially expressed genes (DEGs) in IS and autophagy-related genes (ARGs). Functionally, experiments uncovered that down-regulation of PPP1R15A alleviated oxygen–glucose deprivation/reoxygenation (OGD/R)-mediated inhibition of cell viability and promotion of LDH release, cell apoptosis, autophagy, and inflammation in A172 and SH-SY5Y cells. Simultaneously, silencing PPP1R15A ameliorated the IS progression in the middle cerebral artery occlusion and reperfusion (MCAO/R) rat model. Furthermore, PPP1R15A activated the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway in vivo and in vitro. Rescue experiments indicated that TLR4 inhibitors TAK-242 and NF-κB inhibitors BAY-11-7082 effectively alleviated the malignant progression of IS mediated by overexpression of PPP1R15A. Our data illustrated that PPP1R15A promoted OGD/R-induced cytotoxicity, apoptosis, autophagy, and inflammation by activating the TLR4/NF-κB pathway.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758599","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":"RETRACTION: Aberrant Dynamic Network Connectivity Changes in Comorbid Depression and Overweight/Obesity: Insights From the Triple Network Model","authors":"","doi":"10.1002/jnr.70074","DOIUrl":"https://doi.org/10.1002/jnr.70074","url":null,"abstract":"<p>\u0000 <b>RETRACTION:</b> <span>Zhang, Z.-Q.</span>, <span>Liao, D.</span>, <span>Guo, Z.-P.</span>, <span>Song, S.-S.</span>, and <span>Liu, X.-J.</span> <span>Aberrant Dynamic Network Connectivity Changes in Comorbid Depression and Overweight/Obesity: Insights From the Triple Network Model</span>. <i>Journal of Neuroscience Research</i> <span>102</span>, no. <span>12</span> (<span>2024</span>): e70001, https://doi.org/10.1002/jnr.70001.\u0000 </p><p>The above article, published online on 29 November 2024 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Lawrence S. Sherman; and Wiley Periodicals, LLC. The retraction has been agreed upon after the authors informed the editors that their findings on dynamic functional network connectivity, as presented in Figures 3-7, were not adequately independently validated, thereby undermining the reliability and reproducibility of the results. Furthermore, their ethical approval process was not fully compliant with the standard guidelines. The corresponding author contacted the journal and asked for a retraction, but the authors did not respond when asked to agree to the final retraction wording. The editors consider the results and conclusion of this article to be invalid.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Nonhuman Primate Model to Evaluate Treatments for Long-Gap Ulnar Nerve Injury","authors":"Robert B. Shultz,&nbsp;Franco A. Laimo,&nbsp;Hannah H. Lee,&nbsp;Zarina S. Ali,&nbsp;Ryan Huang,&nbsp;Roy E. Barnewall,&nbsp;Carolyn G. Fetzek,&nbsp;Harry C. Ledebur,&nbsp;D. Kacy Cullen,&nbsp;Kritika S. Katiyar","doi":"10.1002/jnr.70069","DOIUrl":"https://doi.org/10.1002/jnr.70069","url":null,"abstract":"<div>\u0000 \u0000 <p>Among all upper extremity nerves, the ulnar nerve is both the most commonly injured and notoriously difficult to regenerate. Despite this, ulnar nerve injuries remain understudied. Nonhuman primates (NHPs) offer an ideal model for the human upper extremity, but existing NHP nerve trauma literature is biased towards median and radial injury models. To address this, a nonhuman primate ulnar nerve injury model was developed and regeneration assessed following sural nerve autografting using electrophysiological and histological techniques. Unilateral 4 cm ulnar nerve injuries were created at the mid-forearm level, sural nerve autografts were sutured into resulting defects (<i>n</i> = 3), and animals were survived for 6 months. At the terminal time point, intraoperative electrophysiological testing, tissue harvest, and tissue processing were performed. Naïve nerves (<i>n</i> = 5) served as controls. Animals appeared clinically normal throughout the study period, other than an expected decrease in fine hand muscle function. After 6 months, histological and electrophysiological evidence suggested that axons crossed the graft and reached distal muscle targets. However, regenerating nerves exhibited a reduced motor nerve conduction velocity, reduced compound action muscle potential (CMAP) amplitude and area under the curve, increased latency, and increased duration versus naïve controls as expected. Histological analysis revealed reduced axon diameters, thinner myelin sheaths, and smaller muscle fiber cross-sectional areas as compared to controls. At 6 months post-injury, 4 cm ulnar defects bridged with sural autografts show signs of ongoing regeneration and nascent reinnervation. Specific electrophysiological and histological benchmarks for ulnar nerve recovery following clinically relevant autografting are presented.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740533","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":"Transcriptomic Profiling Reveals Injury Responses of Peripheral Glial Cells in Sensory Neuron Microenvironment","authors":"Jiacheng Xu,&nbsp;Jiaxin Jin,&nbsp;Saizhen Lv,&nbsp;Yanyu Pan,&nbsp;Dong Wang,&nbsp;Nimei Shen,&nbsp;Youhua Wang","doi":"10.1002/jnr.70072","DOIUrl":"https://doi.org/10.1002/jnr.70072","url":null,"abstract":"<div>\u0000 \u0000 <p>Schwann cells and satellite glial cells (SGCs) are important peripheral glial cells in the dorsal root ganglion (DRG) and commendable participants in regulating neuronal functions. Herein, through re-analysis of publicly available single-nucleus RNA sequencing data from naïve and injured DRG at 1 and 3 days following sciatic nerve crush, we systematically characterized the transcriptomic alterations in Schwann cells and SGCs. Cell clustering and counting showed that peripheral glial cells occupied a large population after sciatic nerve crush injury. Using differentially expression analysis, we found that apoptosis and immune responses were involved in all these examined peripheral glial cells. Unique glial cells also responded differently to sciatic nerve crush injury, with myelinating Schwann cells characterized by enriched adenosine 5′-monophosphate activated protein kinase (AMPK) metabolic signaling, non-myelinating Schwann cells characterized by enriched tissue-remodeling-related signaling, and SGCs characterized by enriched ion channels. Using single-cell regulatory network inference and clustering (SCENIC) to determine essential transcription factors in specific cell type at the naïve state and at multiple time points after sciatic nerve crush injury, we found that Schwann cells and SGCs possessed their own elevated transcription factor-coding genes, with activating factor 3 (Atf3) commonly highly up-regulated in all peripheral glial cells. This study provides a profiling map of peripheral glial cells at the naïve and injured states, expands the acknowledgment of the molecular background of nerve injury, and can lead to novel strategies to promote sensory nerve regeneration.</p>\u0000 </div>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716594","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":"Metabolic and Structural Alterations in the Motor System Following Spinal Cord Injury: An In-Vivo 1H-MR Spectroscopy Investigation","authors":"Simon Schading-Sassenhausen,&nbsp;Anna Lebret,&nbsp;Kadir Şimşek,&nbsp;Pauline Gut,&nbsp;Sabrina Imhof,&nbsp;Björn Zörner,&nbsp;Roland Kreis,&nbsp;Patrick Freund,&nbsp;Maryam Seif","doi":"10.1002/jnr.70071","DOIUrl":"https://doi.org/10.1002/jnr.70071","url":null,"abstract":"<p>Spinal cord injury (SCI) disrupts spinal tracts and neuronal pathways, including those in the primary motor cortex (M1) and the lumbar cord enlargement (LCE) involved in motor control. This study sought to determine whether metabolite concentrations deviate between SCI and healthy controls (HC) in M1 and LCE using proton magnetic resonance spectroscopy (¹H-MRS) and structural MRI, and if these correlate with clinical impairment. Sixteen chronic SCI (mean age: 54.7 ± 14.8y) and 19 HCs (mean age: 53.2 ± 18.8y) underwent ¹H-MRS to quantify metabolites along with T₁- and T₂*-weighted MRI to assess tissue structural changes. Associations between metabolic and structural changes and clinical impairment were also assessed. Patients showed significant atrophy in both white matter of the LCE (HC: 37.7 ± 4.7 mm², SCI: 33.9 ± 3.7 mm², Δ = −10.1%, <i>p</i> = 0.015) and gray matter (HC: 20.9 ± 2.1 mm², SCI: 19.4 ± 1.5 mm², Δ = −7.2%, <i>p</i> = 0.022). Total N-acetylaspartate (tNAA) with respect to total creatine (tCr) was reduced in M1 of SCI (HC: 1.94 ± 0.21, SCI: 1.77 ± 0.14, ∆ = −8.8%, <i>p</i> = 0.006) and in the LCE (HC: 2.48 ± 0.76, SCI: 1.81 ± 0.80, ∆ = −27.0%, <i>p</i> = 0.02). In conclusion, reduced tNAA/tCr in both the atrophied LCE and M1 suggests widespread neuronal changes including cell atrophy and/or cell loss after injury. These findings provide in vivo evidence for retrograde and trans-synaptic neurodegeneration, which may underline the atrophy observed in the motor system in SCI. Ultimately, this highlights the potential for metabolic and structural biomarkers to improve the monitoring of subtle neurodegeneration following SCI and to enhance future regenerative treatment strategies.</p>","PeriodicalId":16490,"journal":{"name":"Journal of Neuroscience Research","volume":"103 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jnr.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688040","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}