Neuroscience Letters最新文献_第3页

1-Epilupinine enhances cognition and reduces inflammation in scopolamine-induced dementia model mice

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-03-06 DOI: 10.1016/j.neulet.2025.138184

Chenhui Zhang , Jiyi Xu , Fang Xu , Xiaomeng Xie , Tengfei Ji , Chuanyue Wang , Jing Du

{"title":"1-Epilupinine enhances cognition and reduces inflammation in scopolamine-induced dementia model mice","authors":"Chenhui Zhang , Jiyi Xu , Fang Xu , Xiaomeng Xie , Tengfei Ji , Chuanyue Wang , Jing Du","doi":"10.1016/j.neulet.2025.138184","DOIUrl":"10.1016/j.neulet.2025.138184","url":null,"abstract":"<div><div>Dementia is a growing global public health concern. The search for effective anti-dementia drugs with fewer side effects, particularly in the early stages of the disease, is a key focus of current research. Natural compounds like 1-Epilupinine (ELP) may offer therapeutic potential for cognitive improvement and neuroprotection. To assess the potential of ELP in improving dementia and neuroinflammation in a scopolamine-induced dementia model in mice, a mouse model was induced using scopolamine hydrobromide, with Donepezil as the positive control. After five days of treatment, cognitive performance was assessed using the Morris water maze test. Motor function and anxiety-related behaviors were evaluated through the open field test. An inflammatory factor array was employed to measure inflammatory markers in the prefrontal cortex. The Morris water maze showed that the model group treated with scopolamine hydrobromide (1 mg/kg) had significantly fewer platform crossings and longer latency (<em>P</em> < 0.001) while mice treated with ELP (5 mg/kg) exhibited improved performance, with more crossings and reduced latency (<em>P</em> < 0.01), suggesting ELP effectively reversed cognitive deficits. In the open field test, no significant difference of total movement distance was detected in ELP-treated groups, indicating it did not impair motor function. The result of the inflammation factors array detecting showed lower levels of GM-CSF, IFN-γ, IL-2, and IL-23 significantly in the ELP (5 mg/kg) group, suggesting its potential anti-inflammatory properties for the dementia treatment. Therefore, ELP may serve as a promising treatment for early-stage dementia, offering cognitive improvement alongside anti-inflammatory neuroprotection.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"852 ","pages":"Article 138184"},"PeriodicalIF":2.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577966","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}

引用次数: 0

Delayed treatment with TGF-β1 associated neuroprotection in trimethyltin-induced hippocampal neurodegeneration

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-03-04 DOI: 10.1016/j.neulet.2025.138182

Ekaterina V. Fedorova, Irina Yu. Chernomorets, Dmitry A. Fedorov, Vladimir I. Arkhipov

{"title":"Delayed treatment with TGF-β1 associated neuroprotection in trimethyltin-induced hippocampal neurodegeneration","authors":"Ekaterina V. Fedorova, Irina Yu. Chernomorets, Dmitry A. Fedorov, Vladimir I. Arkhipov","doi":"10.1016/j.neulet.2025.138182","DOIUrl":"10.1016/j.neulet.2025.138182","url":null,"abstract":"<div><div>In experiments conducted on Wistar rats, the effects of the multifunctional cytokine TGF-β1 were investigated using a neurodegeneration model induced by a single injection of the neurotoxicant trimethyltin chloride (TMT). Animals in the experimental group received intranasal administration of TGF-β1 on days 7 and 9 following TMT injection. Behavioral tests were performed to assess cognitive function, and three weeks after TMT administration, hippocampal morphology was analyzed using Nissl staining. Additionally, the state of microglia was evaluated through immunohistochemical labeling of IBA1. The results revealed that exogenous TGF-β1 significantly modulated the progression of hippocampal neurodegeneration. In the passive avoidance test, TGF-β1 ameliorated TMT-induced long-term memory impairment and promoted neuronal preservation in the CA1 region of the hippocampus, although no such effect was observed in the CA3 and CA4 regions. Furthermore, TGF-β1 treatment reduced microglial activation levels in the hippocampal CA1 region compared to animals treated with TMT alone. These findings suggest that the multifunctional cytokine TGF-β1 exerts a neuroprotective effect in the context of ongoing neurodegeneration when delivered intranasally to the brain. The cytokine’s ability to regulate microglial activity appears to contribute, at least in part, to its protective properties.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"852 ","pages":"Article 138182"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562282","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}

引用次数: 0

Inflammatory pain modifies reward preferences from larger delayed to smaller immediate rewards in male rats

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-03-04 DOI: 10.1016/j.neulet.2025.138183

Mariana Cerqueira-Nunes , Clara Monteiro , Vasco Galhardo , Helder Cardoso-Cruz

{"title":"Inflammatory pain modifies reward preferences from larger delayed to smaller immediate rewards in male rats","authors":"Mariana Cerqueira-Nunes , Clara Monteiro , Vasco Galhardo , Helder Cardoso-Cruz","doi":"10.1016/j.neulet.2025.138183","DOIUrl":"10.1016/j.neulet.2025.138183","url":null,"abstract":"<div><div>Self-control underlies goal-directed behavior in both humans and rodents. The ability to balance immediate and delayed gratification is essential for fine-tuning decision-making processes to achieve optimal rewards. Although delayed gratification has been extensively studied using human neuropsychological assessments, brain imaging techniques, and preclinical research, the impact of chronic pain on these processes remains poorly understood. In this study, we successfully trained male rats to perform a custom delayed gratification task (DGt) to evaluate time-reward gratification associations. The task required rats to choose between two levers associated with distinct schedules of reward delivery and magnitude. Behavioral performance was assessed within subjects following the induction of inflammatory chronic pain using the complete Freund’s adjuvant (CFA) model. Our findings revealed that CFA-treated rats developed mechanical allodynia and demonstrated a strong preference for small and immediate rewards. In contrast, saline-treated control rats exhibited a more balanced choice profile, indicative of intact self-control. Collectively, these results offer novel insights into how chronic inflammatory pain disrupts time-reward preferences and impairs self-control mechanisms.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"852 ","pages":"Article 138183"},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551002","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}

引用次数: 0

MiR-222-3p regulates methamphetamine-induced behavioral sensitization through PP2A–AKT signaling pathway in the dorsal striatum of male mice MiR-222-3p通过PP2A-AKT信号通路调节雄性小鼠背侧纹状体中甲基苯丙胺诱导的行为致敏。

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-03-01 DOI: 10.1016/j.neulet.2025.138181

Gang Chen , Xingyao Chen , Wei Han , Baoyao Gao , Min Liang , Tao Li , Xinshe Liu

{"title":"MiR-222-3p regulates methamphetamine-induced behavioral sensitization through PP2A–AKT signaling pathway in the dorsal striatum of male mice","authors":"Gang Chen , Xingyao Chen , Wei Han , Baoyao Gao , Min Liang , Tao Li , Xinshe Liu","doi":"10.1016/j.neulet.2025.138181","DOIUrl":"10.1016/j.neulet.2025.138181","url":null,"abstract":"<div><div>Drug addiction is a chronic and recurrent brain disease. Our previous research demonstrated that the B subunit of phosphatase 2A (PP2A/B) increased in the dorsal striatum (DS) of methamphetamine (METH)-sensitized mice. Interestingly, studies indicate that PP2A/B can also interplay with microRNA (miRNA). In this study, we investigated seven miRNAs that have been reported to potentially interplay with PP2A/B, and our results showed that miR-222-3p significantly decreased in the DS of METH-sensitized mice. We further used dual-luciferase reporter assay to clarify the regulatory relationship between miR-222-3p and PP2A/B mRNA, and we also constructed adeno-associated virus (AAV) to overexpress miR-222-3p in the DS to further examine the influence of miR-222-3p on METH-induced behavioral sensitization. Our results demonstrated that miR-222-3p did interplay with PP2A/B mRNA and overexpressed miR-222-3p could significant attenuate METH-induced behavioral sensitization. At the same time, overexpressed miR-222-3p could reverse the change in the PP2A–AKT signaling pathway in the DS of METH-sensitized mice. Our results indicate that overexpression of miR-222-3p in the DS might attenuate METH-induced behavioral sensitization through the PP2A–AKT signaling pathway.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"852 ","pages":"Article 138181"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542789","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}

引用次数: 0

Role of pentosidine accumulation in stress-induced social behavioral deficits

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-02-27 DOI: 10.1016/j.neulet.2025.138180

Mayuko Masada , Kazuya Toriumi , Kazuhiro Suzuki , Mitsuhiro Miyashita , Masanari Itokawa , Makoto Arai

{"title":"Role of pentosidine accumulation in stress-induced social behavioral deficits","authors":"Mayuko Masada , Kazuya Toriumi , Kazuhiro Suzuki , Mitsuhiro Miyashita , Masanari Itokawa , Makoto Arai","doi":"10.1016/j.neulet.2025.138180","DOIUrl":"10.1016/j.neulet.2025.138180","url":null,"abstract":"<div><div>The mechanisms underlying schizophrenia, a psychiatric disorder characterized by significant social and behavioral impairments, remain poorly understood. However, glycation stress, driven by the accumulation of advanced glycation end products (AGEs) such as pentosidine, has been implicated in its pathogenesis. Therefore, this study aimed to explore the role of pentosidine in stress-induced social behavioral deficits using a mouse model of social defeat stress (SDS). Mice exposed to SDS displayed individual differences in sociability, and were categorized into stress-susceptible and stress-resilient phenotypes based on their social interaction ratio. Pentosidine levels were significantly elevated in the plasma and the prefrontal cortex (Pfc) of the susceptible group, which correlated with increased social avoidance and decreased interaction times. Administration of pyridoxamine, an AGE synthesis inhibitor, during SDS exposure mitigated these behavioral deficits, and suppressed pentosidine accumulation in both the plasma and Pfc. These findings provide the first evidence linking pentosidine accumulation to stress susceptibility, indicating the involvement of a molecular pathway through which glycation stress influences social behavior. Future studies should further elucidate the mechanisms underlying the effects of pentosidine on behavior, and explore its broader implications in psychiatric disorders.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"852 ","pages":"Article 138180"},"PeriodicalIF":2.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537480","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}

引用次数: 0

A novel prefrontal cortex and hippocampus combined brain slice based on in vivo diffusion tensor imaging of healthy male rats

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-02-24 DOI: 10.1016/j.neulet.2025.138171

Lijun Zhang , Qian Zhou , Guanghao Zhang , Changzhe Wu , Wei Rong , Shiji He , Xiaolin Huo , Cheng Zhang

{"title":"A novel prefrontal cortex and hippocampus combined brain slice based on in vivo diffusion tensor imaging of healthy male rats","authors":"Lijun Zhang , Qian Zhou , Guanghao Zhang , Changzhe Wu , Wei Rong , Shiji He , Xiaolin Huo , Cheng Zhang","doi":"10.1016/j.neulet.2025.138171","DOIUrl":"10.1016/j.neulet.2025.138171","url":null,"abstract":"<div><div>The pathway between the prefrontal cortex (PFC) and hippocampus (HPC) has been associated with various psychiatric disorders. While hippocampal brain slices are extensively utilized, their use has traditionally been constrained in studying long connectivity between PFC and HPC due to nerve fiber rupture during the slicing process. Consequently, optimizing brain slice preparation is crucial. The experiment consisted of three phases. Initially, the structural connection of the PFC-HPC pathway was examined using diffusion tensor imaging (DTI) data from healthy male rats. Subsequently, combined PFC-HPC brain slices were created through vibratome based on imaging acquisition. Finally, the morphology and electrophysiology of the combined brain slices were analyzed. DTI findings revealed numerous nerve fibers linking the two brain regions in the rat brain. Subsequently, a successful preparation of combined PFC-HPC brain slices cut at a 7 – 8° angle relative to the middle sagittal plane was achieved using a vibratome. Hematoxylin and eosin staining results confirmed that PFC-HPC fibers remained well-preserved in the combined brain slice. Electrophysiological recordings indicated that synchronized neuronal activity occurred in the HPC upon PFC stimulation, which depended on hippocampal activity and the integrity of PFC-to-HPC connectivity. A novel procedure for the successful preparation of healthy combined HPC-PFC brain slices, maintaining a complete fiber bundle connection between PFC and HPC, is proposed. This methodology enhances the understanding of the preservation of PFC-HPC connectivity in specific angled brain slice preparations, thereby facilitating neuroscience research focused on the longrange circuitry of subregions of interest.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138171"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509159","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}

引用次数: 0

Electroacupuncture inhibits oxidative stress and improves cognitive function by downregulating the Ang II/AT1R/NOX axis in chronic cerebral ischemia rats

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-02-23 DOI: 10.1016/j.neulet.2025.138179

Qi Ai , Jurui Wei , Bijun Luo , Zixuan Wang , Jun Dong , Jiumei Zhao , Wenqing Xu , Lin Chen , Wenyao Fang , Songjie Zhu

{"title":"Electroacupuncture inhibits oxidative stress and improves cognitive function by downregulating the Ang II/AT1R/NOX axis in chronic cerebral ischemia rats","authors":"Qi Ai , Jurui Wei , Bijun Luo , Zixuan Wang , Jun Dong , Jiumei Zhao , Wenqing Xu , Lin Chen , Wenyao Fang , Songjie Zhu","doi":"10.1016/j.neulet.2025.138179","DOIUrl":"10.1016/j.neulet.2025.138179","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to explore the effects of Electroacupuncture (EA) on chronic cerebral ischemia (CCI).</div></div><div><h3>Methods</h3><div>A CCI rat model was established by blocking the common carotid arteries. Model rats were treated with EA at the “Baihui” (GV20) and “Dazhui” (GV14) acupoints and/or ARB. Ang II and AT1R expression in the artery and hippocampal tissues was determined. Immunohistochemistry staining was used to detect RECA-1 expression in hippocampal tissues. NOX2, NOX4, SOD1, SOD2, ROS, and MDA levels were examined. Morris water maze and TUNEL staining were used to explore the effects of EA on cognitive impairment and apoptosis, respectively.</div></div><div><h3>Results</h3><div>Ang II and AT1R levels were reduced by EA in CCI rats. RECA-1 expression was reduced in model rats, while EA and ARB increased its expression. EA inhibited oxidative stress in CCI rats. Besides, EA improved cognitive impairment in CCI rats. Apoptosis in the hippocampal tissues of CCI rats was inhibited by EA treatment. Furthermore, inhibition of Ang II/AT1R/NOX axis promoted the therapeutic effects of EA on oxidative stress and cognitive impairment in model rats.</div></div><div><h3>Conclusions</h3><div>EA treatment at the “Baihui” (GV20) and “Dazhui” (GV14) acupoints is effective against CCI-induced cognitive impairment and oxidative stress by downregulating Ang II/AT1R/NOX axis.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138179"},"PeriodicalIF":2.5,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143502890","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}

引用次数: 0

Nicotinamide adenine dinucleotide alleviates neuroinflammation in rats with traumatic brain injury

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-02-22 DOI: 10.1016/j.neulet.2025.138178

Huancheng Wu , Mengli Jin , Jiandong Hu , Fenge Li

{"title":"Nicotinamide adenine dinucleotide alleviates neuroinflammation in rats with traumatic brain injury","authors":"Huancheng Wu , Mengli Jin , Jiandong Hu , Fenge Li","doi":"10.1016/j.neulet.2025.138178","DOIUrl":"10.1016/j.neulet.2025.138178","url":null,"abstract":"<div><h3>Objective</h3><div>To characterize the pathology and pathophysiological processes within 6 h after Traumatic brain injury (TBI) in rats, elucidate the neuroprotective effects and the underlying mechanisms of Nicotinamide Adenine Dinucleotide (NAD) in the early stage of TBI to explore the feasibility and clinical benefits of applying NAD directly to the localized injury after TBI.</div></div><div><h3>Material and Methods</h3><div>54 male Sprague-Dawley (SD) rats aged 6–8 weeks were randomly assigned equally to three groups, sham-operated surgery (SO) with saline treatment (SO + Saline), TBI with saline treatment (TBI + Saline), and TBI with 10 μM NAD treatment (TBI + NAD). The whole brain tissues were collected at 1, 3, and 6 h following the procedure. Levels of biomarkers for TBI including S100β, TNF-α, occludin, PPARβ/δ were measured.</div></div><div><h3>Results</h3><div>Significant neuroinflammation was observed in the rat brains after TBI, which peaked at 3 h following injury. Significant changes in S100β, TNF-α, PPARβ/δ, and occluding were also observed. Treatment with NAD significantly alleviated neuroinflammation at 1 h following TBI.</div></div><div><h3>Conclusions</h3><div>TBI caused severe neuroinflammation in rat brains, which peaked at 3 h following injury. Treatment with NAD alleviated neuroinflammation in TBI rats.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"852 ","pages":"Article 138178"},"PeriodicalIF":2.5,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493131","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}

引用次数: 0

Investigating the antidepressant effects of amantadine combined with amitriptyline in a chronic unpredictable mild stress model in mice

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-02-19 DOI: 10.1016/j.neulet.2025.138169

Vijay Kumar, Gaurav Doshi

{"title":"Investigating the antidepressant effects of amantadine combined with amitriptyline in a chronic unpredictable mild stress model in mice","authors":"Vijay Kumar, Gaurav Doshi","doi":"10.1016/j.neulet.2025.138169","DOIUrl":"10.1016/j.neulet.2025.138169","url":null,"abstract":"<div><div>Amantadine, an N-Methyl-D-Aspartate (NMDA) receptor antagonist traditionally used as an antiviral drug, was investigated for its potential antidepressant effect in combination with amitriptyline, a well-established tricyclic antidepressant, in a Chronic Unpredictable Mild Stress (CUMS) animal model of depression. This study aimed to evaluate the efficacy of this drug combination in alleviating depression-like symptoms. Behavioral assessments were conducted using the Forced Swim Test, Tail Suspension Test, Actophotometer test, and Sucrose Preference Test to measure depressive effect. Further biochemical analyses revealed a marked reduction in Brain-derived neurotrophic factor (BDNF) and norepinephrine (NE) levels in the CUMS group compared with the control group. BDNF is crucial for neuroplasticity, synaptic regulation, and neuronal survival and its reduced level is linked to the development of depression. Similarly, NE, a key neurotransmitter involved in mood regulation, is often decreased in depressive states. Conversely, the CUMS group exhibited a significant increase in Tumour necrosis factor-alpha (TNF-α) levels, indicating enhanced inflammatory response, which is also associated with depression. Treatment with the combination of amantadine and amitriptyline resulted in a significant antidepressant-like effect, as demonstrated by improved behavioral parameters and normalization of this biomarker the increase in BDNF and NE levels along with a reduction in TNF-α.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138169"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465235","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}

引用次数: 0

Using MRI to Determine Drug Concentration in Convection-Enhanced Delivery: A Proof-of-Concept study

IF 2.5 4区医学

Neuroscience Letters Pub Date : 2025-02-19 DOI: 10.1016/j.neulet.2025.138170

Xiaojie Ding , Ming Qi , Yuan Zhou , Ying Qi , Di Chen , Xinyu Yang , Chunxia Ji , Yu Yao

{"title":"Using MRI to Determine Drug Concentration in Convection-Enhanced Delivery: A Proof-of-Concept study","authors":"Xiaojie Ding , Ming Qi , Yuan Zhou , Ying Qi , Di Chen , Xinyu Yang , Chunxia Ji , Yu Yao","doi":"10.1016/j.neulet.2025.138170","DOIUrl":"10.1016/j.neulet.2025.138170","url":null,"abstract":"<div><div>Convection-enhanced delivery (CED) bypasses the blood–brain barrier and avoids systemic exposure to the drug. However, systemic pharmacokinetic characteristics of a drug cannot be applied when delivered via CED. This study aims to provide a first proof-of-concept framework for noninvasively evaluating pharmacokinetics in CED. We investigated local concentration and the distribution of a gadolinium-based contrast agent in rat brains using magnetic resonance imaging (MRI). Standards of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) were scanned on a 7.0 T MRI system in rat brain tissue suspension. <em>T</em><sub>1</sub> values were mapped and <em>T</em><sub>1</sub> relaxivity of Gd-DTPA was calculated. Subsequently, evaluation in live animals was performed by infusing Gd-DTPA into the rat striatum followed by scans for <em>T</em><sub>1</sub> mapping. The quantitative relationship between imaging data and Gd-DTPA concentration deduced from standard scans was used to determine the voxel-level concentration of Gd-DTPA in rat brains. Concentration maps were constructed from voxel-level concentration data. The Gd-DTPA concentration in tissue suspension and 1/ <em>T</em><sub>1</sub> showed a linear relationship with <em>R</em><sup>2</sup> of 0.9919 (p < 0.0001). The <em>T</em><sub>1</sub> relaxivity of Gd-DTPA at the experimental condition was 4.199 mM<sup>−1</sup> s<sup>−1</sup>. Within the rat brain parenchyma, the mean volume of distribution to initial volume ratio (Vd/Vi) of Gd-DTPA was calculated to be 6.02. Notably, the infusion center’s concentration exhibited a decreasing pattern, while the peripheral region’s concentration remained relatively stable over the observed duration. This study showed the spatial distribution of Gd-DTPA concentration and its temporal change, suggesting that using MRI to determine the Gd-DTPA concentration is feasible with good accuracy and data quality.</div></div>","PeriodicalId":19290,"journal":{"name":"Neuroscience Letters","volume":"851 ","pages":"Article 138170"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472585","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}

引用次数: 0