{"title":"Application of Diffusional Kurtosis Imaging on Normal-Appearing White Matter in Cerebral Small Vessel Disease.","authors":"Yue-Lin Guo, Si-Lan Chen, Hai-Bing Rao, Ling-Mei Kong, Wei-Jia Li, Qi-Ze Liu, Feng-Yu Liu, Yu Wang, Wen-Bin Zheng","doi":"10.31083/JIN25521","DOIUrl":"https://doi.org/10.31083/JIN25521","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the diagnostic potential of diffusional kurtosis imaging (DKI) parameters in detecting pathological alterations in the normal-appearing white matter (NAWM) associated with cerebral small vessel disease (CSVD).</p><p><strong>Methods: </strong>A total of 56 patients diagnosed with CSVD were enrolled, all exhibiting confirmed lacunar infarction in the corticospinal tract (CST) as verified by conventional magnetic resonance imaging. A control group of 24 healthy individuals who exhibited no discernible abnormalities on conventional magnetic resonance imaging (MRI) scans was also included. The following DKI parameters were recorded, including mean kurtosis (MK), axial kurtosis (Ka), and radial kurtosis (Kr). Regions of interest were placed at representative levels of the CST on the affected side, encompassing the pons, anterior part of the posterior limb of the internal capsule (PLIC), corona radiata, and subcortex.</p><p><strong>Results: </strong>Variations in MK, Ka, and Kr values in the pons, anterior part of the PLIC, corona radiata, and subcortex of the control group were observed. Notably, the MK and Kr values of the normal-appearing pons in CSVD patients were significantly elevated compared with the control group. The MK, Ka value of the normal-appearing anterior part of the PLIC was significantly higher in the CSVD group than in the control group. The Kr value of the normal-appearing corona radiata exhibited a significant elevation in CSVD patients compared with the control group. Lastly, patients with CSVD displayed lower Ka values and higher Kr values in the normal-appearing subcortex compared with the control group.</p><p><strong>Conclusions: </strong>DKI is an effective tool for assessing NAWM in patients with CSVD. These findings potentially offer novel insights into the prognosis of CSVD and serve as a foundational platform for future DKI studies on NAWM in other diffuse brain lesions.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"25521"},"PeriodicalIF":2.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523452","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}
Faming Zhou, Guanghui Chen, Xiaoli Li, Xiaodong Yu, Yinyin Yang
{"title":"Lactylation of PLBD1 Facilitates Brain Injury Induced by Ischemic Stroke.","authors":"Faming Zhou, Guanghui Chen, Xiaoli Li, Xiaodong Yu, Yinyin Yang","doi":"10.31083/JIN25949","DOIUrl":"https://doi.org/10.31083/JIN25949","url":null,"abstract":"<p><strong>Background: </strong>Ischemic stroke is a prevalent global condition and its associated brain damage poses a significant threat to patient survival and outcomes. The underlying mechanisms of ischemic stroke-induced brain injury remain elusive, necessitating further investigation.</p><p><strong>Methods: </strong>Ischemic stroke models were established using middle cerebral artery occlusion (MCAO) in animals and oxygen-glucose deprivation and reperfusion (OGD-R) in cells. Phospholipase B domain-containing protein 1 (PLBD1) expression in these models was assessed <i>via</i> western blotting analysis, reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), and cell immunofluorescence. A comprehensive evaluation, incorporating cellular lactate dehydrogenase (LDH) release assays, glycolysis metabolism kits, RT-qPCR, western blotting, triphenyl tetrazolium chloride (TTC) staining, neurological scoring, brain tissue water content measurement, and creatine kinase-MB (CK-MB) analysis, was conducted to determine the impact of PLBD1 on brain injury. Potential lactylation sites in PLBD1 were predicted using the DeepKla database, with western blotting and co-immunoprecipitation (Co-IP) confirming the lactylation site.</p><p><strong>Results: </strong>PLBD1 was significantly upregulated in the brain tissue of MCAO animal models and OGD-R-treated cells. PLBD1 knockdown markedly mitigated OGD-R-induced cellular injury, suppressed glycolysis <i>in vitro</i>, and reversed MCAO-induced brain damage <i>in vivo</i>. Furthermore, lactylation at the K155 site of PLBD1 enhanced its expression in response to elevated lactate levels following OGD-R treatment. These results indicated that the upregulation of PLBD1 <i>via</i> K155 site lactylation plays a pivotal role in exacerbating ischemic stroke-induced brain damage.</p><p><strong>Conclusion: </strong>Targeting the lactate/PLBD1 axis presents a promising therapeutic strategy for ischemic stroke management.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"25949"},"PeriodicalIF":2.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523467","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":"Auditory Cognitive Impairment Reflects Source Localization of the P300 ERP Component in MBI Patients: The sLORETA Investigation.","authors":"Mohammed Faruque Reza, Tahamina Begum","doi":"10.31083/JIN25906","DOIUrl":"https://doi.org/10.31083/JIN25906","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the differences between the source localization of the P300 event-related potential (ERP) component among the healthy and mild brain injury (MBI) patient population using standardized low-resolution electromagnetic tomography (sLORETA).</p><p><strong>Methods: </strong>Thirty-eight participants were divided into control (n = 19) and MBI (n = 19) groups. Control participants were normal, healthy people, and participants with MBI were assigned into two groups: MBI 1st Test (7 days after a road traffic accident (RTA)) and MBI 2nd Test (2-6 months after RTA with the same participants of the 1st Test group). The 128-ERP nets were used on the heads of the participants during the experiments. Under the auditory oddball paradigm, all participants silently counted the target tones, while ignoring the standard tones. This study used the sLORETA tool in the Net Station software for the source localization of the P300 ERP component. The Mann-Whitney U test was used to compare intensities between groups, while the Wilcoxon Signed-Rank test was applied for paired observations within groups.</p><p><strong>Results: </strong>Standard stimuli evoked P300 sources in the superior frontal gyrus (BA11) of the right frontal lobe in the control group, the superior temporal gyrus (BA38) of the right temporal lobe in the MBI 1st Test group, and the inferior frontal gyrus (BA47) of the left frontal lobe in the MBI 2nd Test group. Meanwhile, target stimuli evoked P300 sources at BA11 for all groups but in different gyrus: the superior frontal gyrus, orbital gyrus, and rectal gyrus in the control, MBI 1st Test, and MBI 2nd Test groups, respectively. In addition, there were significant differences in dipole intensities between and within groups among control and MBI patients in both standard and target stimuli.</p><p><strong>Conclusion: </strong>P300 source localization was shifted presumably due to the auditory cognitive impairment, and the dipole intensities were significantly higher in the MBI group than in the control group, indicating that the MBI group compensated for both standard and target tone stimuli, reflected in the sLORETA investigation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"25906"},"PeriodicalIF":2.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523453","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}
David Goldeck, Lilly Oettinger, Tamas Fülöp, Claudia Schulte, Klaus Hamprecht, Daniela Berg, Walter Maetzler, Graham Pawelec
{"title":"Frequencies of Circulating Immune Cells in Patients with Parkinson's Disease: Correlation with MDS-UPDRS Scores.","authors":"David Goldeck, Lilly Oettinger, Tamas Fülöp, Claudia Schulte, Klaus Hamprecht, Daniela Berg, Walter Maetzler, Graham Pawelec","doi":"10.31083/JIN26393","DOIUrl":"https://doi.org/10.31083/JIN26393","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's Disease (PD) is associated with dysregulated/chronic inflammation. The immune system has multiple roles including beneficial effects such as clearing alpha synuclein aggregates. However, peripheral immune cells entering the brain may also contribute to inflammation and neurodegeneration. To identify which cells might have a negative impact and could be potential therapeutic targets, we compared immune signatures of patients and healthy controls.</p><p><strong>Methods: </strong>Multicolor flow cytometry was used to determine the frequencies of major immune cell subsets in peripheral blood mononuclear cells (PBMCs) of PD patients and controls. Because of the major impact of Cytomegalovirus (CMV) infection on the distribution of immune cell subsets, particularly cluster of differentiation (CD)8+ T-cells, all participants were tested for CMV seropositivity.</p><p><strong>Results: </strong>Although the cohort of 35 PD patients exhibited the well-established T-cell differentiation signature driven by CMV infection, there were no differences in the frequencies of differentiated or pro-inflammatory T-cells, B-cells or natural killer cells (NK-cells) attributable to the disease. However, percentages of myeloid-derived suppressor cells (MDSCs) were higher in PD patients than controls. Moreover, percentages of CD14+CD16+ (intermediate) monocytes expressing the C-C chemokine receptor type 5 (CCR5) correlated with disease severity assessed by the Movement Disorder Society's revised version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and disease duration.</p><p><strong>Conclusions: </strong>A comprehensive evaluation of the major subsets of circulating immune cells in PD patients revealed differences in myeloid cells between PD and healthy controls and some correlation of monocyte abundance with disease severity.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"26393"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523386","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}
Na Kyung Lee, Duk L Na, Hee Jin Kim, Hyemin Jang, Jason K Sa, Bae Sung Ko, Jong Wook Chang
{"title":"Prolonged Chronic Cerebral Hypoperfusion Does not Exacerbate Tau Pathology in a Tauopathy Mouse Model.","authors":"Na Kyung Lee, Duk L Na, Hee Jin Kim, Hyemin Jang, Jason K Sa, Bae Sung Ko, Jong Wook Chang","doi":"10.31083/JIN26108","DOIUrl":"https://doi.org/10.31083/JIN26108","url":null,"abstract":"<p><strong>Background: </strong>Several preclinical studies have reported elevated levels of tau following the induction of chronic cerebral hypoperfusion (CCH) in Alzheimer's disease mouse models. The objective of this study was to first induce CCH in a mouse model of tauopathy over an extended period of up to 6 months and to subsequently investigate the effects of CCH on tau accumulation and alterations in the transcriptome.</p><p><strong>Methods: </strong>Three-month-old P301S tauopathy mice were randomly allocated to either a Sham or CCH group. The common carotid arteries (CCAs) of the CCH group were bilaterally implanted using 0.75-mm inner diameter ameroid constrictors. Prior to surgery, Doppler ultrasound imaging was acquired, with follow-up imaging at 1, 3, and 6 months postoperatively. Brain tissue samples were obtained, and hemispheres were dissected and divided for separate analysis.</p><p><strong>Result: </strong>No significant differences in phosphorylated and total tau protein levels were found in either Sham or CCH left cortical hemispheres or hippocampal lysates. Immunohistochemical staining of phosphorylated tau in the right hemisphere revealed similar findings. Compared with the Sham group, transcriptomic deconvolution revealed a significant reduction of memory B cells in the CCH group (<i>p</i> = 0.029).</p><p><strong>Conclusion: </strong>To clarify the effects of chronic hypoperfusion on tau pathology, more than one surgical method of hypoperfusion should be used in future studies.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"26108"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523567","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}
Ola Mohamed-Fathy Kamal, Doddy Denise Ojeda-Hernández, Belén Selma-Calvo, María Soledad Benito-Martín, Sarah de la Fuente-Martín, Marina García-Martín, Teresa Larriba-González, Francisco Sancho-Bielsa, Jordi A Matias-Guiu, Jorge Matias-Guiu, Ulises Gómez-Pinedo
{"title":"Technical Assessment of Motor and Behavioral Tests in Rodent Models of Multiple Sclerosis.","authors":"Ola Mohamed-Fathy Kamal, Doddy Denise Ojeda-Hernández, Belén Selma-Calvo, María Soledad Benito-Martín, Sarah de la Fuente-Martín, Marina García-Martín, Teresa Larriba-González, Francisco Sancho-Bielsa, Jordi A Matias-Guiu, Jorge Matias-Guiu, Ulises Gómez-Pinedo","doi":"10.31083/JIN26429","DOIUrl":"https://doi.org/10.31083/JIN26429","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a neurodegenerative disorder characterized by progressive motor and cognitive impairments, affecting millions worldwide. It significantly reduces patients' quality of life and imposes a burden on health systems. Despite advances in understanding MS, there is no cure, highlighting the need for effective therapeutic strategies. Preclinical animal models are critical for gaining insights into MS pathophysiology and treatments. However, these models fail to fully replicate the complexity of human MS, making it essential to choose appropriate models and behavioral tests to evaluate their efficacy.</p><p><strong>Purpose: </strong>This review examines various motor and cognitive behavioral tests used in preclinical MS models, discussing their strengths and limitations. The goal is to guide researchers in selecting the most appropriate tests for their models, while providing insights into how these tests are performed and analyzed.</p><p><strong>Methods: </strong>We reviewed motor and cognitive behavioral tests used in MS models, detailing test procedures and evaluating their advantages and disadvantages.</p><p><strong>Results: </strong>This review offers a comprehensive overview that aids researchers in choosing the most suitable tests for their studies, improving the accuracy and reliability of preclinical MS research.</p><p><strong>Conclusions: </strong>Understanding the strengths and limitations of these tests is crucial for making informed decisions, leading to better experimental designs and, ultimately, more effective therapeutic interventions for MS.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"26429"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523654","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}
Yin-Yue Nie, Lu-Yue Huang, Lu-Chuan Wang, Pei Zeng, Chao Gong, Lin Song, Jin Guo, Shaobo Zhou
{"title":"Vitamin D3 Treatment Reduces Epileptic Neuronal Damage by Inhibiting Apoptosis and Increasing Vitamin D Receptor Expression in an <i>In Vivo</i> Epileptic Model.","authors":"Yin-Yue Nie, Lu-Yue Huang, Lu-Chuan Wang, Pei Zeng, Chao Gong, Lin Song, Jin Guo, Shaobo Zhou","doi":"10.31083/JIN25483","DOIUrl":"https://doi.org/10.31083/JIN25483","url":null,"abstract":"<p><strong>Background: </strong>Vitamin D (VitD) deficiency is prevalent in more than half of patients treated with antiepileptic drugs. The number of seizures decreases by more than 40% after vitamin D3 supplementation. This study aimed to investigate the antiepileptic effects of vitamin D3 by using an <i>in vivo</i> epileptic model.</p><p><strong>Method: </strong>Sprague-Dawley rats received pentylenetetrazole (i.p.) treatment to induce epilepsy and were then treated with sodium valproate, VitD, or a combination of VitD and paricalcitol.</p><p><strong>Results: </strong>Vitamin D3 treatment improved epileptic behavior, as evidenced by increased latency time and a significant reduction in epileptic scores on the seventh day after pentylenetetrazole challenge. Improvements in cell morphology and reduced neuronal damage were observed as well as decreased apoptosis rates caused by epilepsy. Although no significant changes in the calcium-sensing receptor (CaSR) were observed in any group, the level of VitD receptor (VDR) significantly increased in groups treated with vitamin D3 alone, and with paricalcitol and sodium valproate.</p><p><strong>Conclusions: </strong>The study demonstrated the effect of vitamin D3 on reducing neuronal damage caused by epilepsy. The neuroprotective effects of vitamin D3 treatment may be attributed to the inhibition of cell apoptosis and the increase in the expression of VitD receptors induced by epilepsy.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"25483"},"PeriodicalIF":2.5,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523665","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":"Advances in the Treatment of Epilepsy by Electrostimulation of the Pulvinar.","authors":"Bingyang Shan, Yang Dai, Quanlei Liu, Changkai Hou, Yihe Wang, Penghu Wei, Guoguang Zhao","doi":"10.31083/JIN22572","DOIUrl":"https://doi.org/10.31083/JIN22572","url":null,"abstract":"<p><p>Neuroregulatory therapy, encompassing deep brain stimulation and responsive neurostimulation, is increasingly gaining attention for the treatment of drug-resistant temporal and occipital lobe epilepsy. Beyond the approved anterior nucleus of the thalamus, the pulvinar nucleus of the thalamus is a potential stimulation target. Through a confluence of animal studies, electrophysiological research, and imaging studies, the pulvinar has been identified as having extensive connections with the visual cortex, prefrontal cortex, limbic regions, and multimodal sensory associative areas, playing a pivotal role in multisensory integration and serving as a propagation node in both generalized and focal epilepsy. This review synthesizes recent research on the pulvinar in relation to cortical and epileptic networks, as well as the efficacy of neuroregulatory therapy targeting the pulvinar in the treatment of temporal and occipital lobe epilepsy. Further research is warranted to elucidate the differential therapeutic effects of stimulating various subregions of the pulvinar and the specific mechanisms underlying the treatment of epilepsy through pulvinar stimulation.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"22572"},"PeriodicalIF":2.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523448","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":"Research Progress in the Pathogenesis of Cognitive Dysfunction in White Matter Hyperintensities: A Narrative Review.","authors":"Ni-Na Song, Jing-Yuan Yu, Chao Wang, Xue-Qi Wu, Guo-Zhao Ma, Xiao-Ying Yuan, Xu-Gang Wang","doi":"10.31083/JIN24840","DOIUrl":"https://doi.org/10.31083/JIN24840","url":null,"abstract":"<p><p>Cerebral small vessel disease is a common disease endangering human health due to its insidious and repeated onset and progressive aggravation. White matter hyperintensities (WMHs) are one of the classic imaging markers of cerebral small vessel disease. The term 'WMHs' was first proposed by Hachinski in 1987. The WMHs in our study mainly refer to cerebral white matter damage caused by various vascular factors, known as vascularized white matter hyperintensity. WMHs are significantly correlated with stroke, cognitive dysfunction, emotional disturbance, and gait abnormality, and have drawn widespread attention. This article reviews the research progress on the pathogenesis of cognitive dysfunction associated with WMHs and provides a theoretical reference for understanding the pathogenesis of WMHs and the early assessment of associated cognitive dysfunction.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"24 2","pages":"24840"},"PeriodicalIF":2.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523594","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}