Brain Research最新文献

{"title":"Prednisolone attenuates seizure severity and neuroinflammation in a pentylenetetrazole-induced acute epilepsy model","authors":"Rafael Bremm Padilha ,&nbsp;Gabriel de Lima Rosa ,&nbsp;Edson Fernando Müller Guzzo ,&nbsp;Amanda Muliterno Domingues Lourenço de Lima ,&nbsp;Gabriela Lazzarotto ,&nbsp;Ana Carolina Sulzbach ,&nbsp;Maria Elisa Calcagnotto ,&nbsp;Adriana Simon Coitinho","doi":"10.1016/j.brainres.2025.149672","DOIUrl":"10.1016/j.brainres.2025.149672","url":null,"abstract":"<div><div>Epilepsy is a brain disorder characterized by alterations in the neuronal environment that predispose individuals to spontaneous and recurrent epileptic seizures. One of the major challenges in recent years has been the accurate diagnosis and appropriate pharmacological management of the condition. When seizures are not well controlled, individuals may develop status epilepticus, a condition with an unfavorable prognosis that requires immediate attention and treatment. Furthermore, approximately 30 % of patients are refractory to conventional treatments. In this study, we evaluated the effects of prednisolone in an acute animal model of epileptic seizures induced by pentylenetetrazole (PTZ) at doses of 1 mg/kg and 5 mg/kg. We analyzed the severity of epileptic seizures and the modulation of pro-inflammatory cytokines in treated animals. Four treatment groups were used: saline solution, diazepam (2 mg/kg), prednisolone (1 mg/kg), and prednisolone (5 mg/kg). The animals were treated, and after 30 min, PTZ (60 mg/kg) was administered. Levels of the cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured in the hippocampus and prefrontal cortex. Animals treated with prednisolone exhibited less severe epileptic seizures compared to the saline group, along with reduced levels of pro-inflammatory cytokines, particularly in the prefrontal cortex. Some animals were also assessed using EEG. Consistent with our previous studies, prednisolone demonstrated an anticonvulsant effect at doses of 1 mg/kg and 5 mg/kg in the acute PTZ-induced seizure model.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1860 ","pages":"Article 149672"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911867","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":"Method for cryopreservation of brainstem pons and medulla oblongata tissue from Sprague Dawley rats for establishing primary mixed neuron-glia cell cultures","authors":"Nicole M. Nalley,&nbsp;Sophia R. Antonopoulos Raithel,&nbsp;Daniela Silva Torres,&nbsp;Paul L. Durham","doi":"10.1016/j.brainres.2025.149665","DOIUrl":"10.1016/j.brainres.2025.149665","url":null,"abstract":"<div><div>Primary cultures of brainstem tissue can be used to investigate cellular and molecular mechanisms involved in disease pathology and to identify novel therapeutic targets that modulate neuron and glial cell activities. However, preparation of primary cultures from rodent embryos or neonatal animals is labor-intensive, and it can be difficult to produce high-quality consistent cultures. To overcome these issues, cryopreservation can be used to obtain standardized, high-quality stocks of brainstem neuronal and glial cells. We present a simplified cryopreservation method for establishing primary cell cultures of pons and medulla oblongata tissue from Sprague-Dawley neonates, using a 90:10 (v/v) fetal bovine serum/dimethyl sulfoxide cell freezing medium. Cryopreserved brainstem cells stored for up to one year in liquid nitrogen exhibited similar neuronal and glial cell morphology, cell ratios, and viability when compared to fresh cultures. The expression of proteins in neurons and glial cells implicated in pain signaling and central sensitization agreed with their reported subcellular localization. Elevated intracellular calcium levels were observed in neurons and glia in response to ATP. This method for the preparation and cryopreservation of brainstem cells for establishing primary neuron-glia cultures similar to fresh preparations, is straightforward, can be utilized for biochemical, cellular, and molecular studies, increases reproducibility, requires no special equipment or reagents, saves laboratory resources including time and money, reduces the number of animals used in research, and increases flexibility in study design.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1860 ","pages":"Article 149665"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143936862","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":"GBE1 alleviates MPTP-induced PD symptoms in mice by enhancing glycolysis and oxidative phosphorylation","authors":"Hongyan Chen ,&nbsp;Hao Ding ,&nbsp;Dongya Huang ,&nbsp;Shuo Wu","doi":"10.1016/j.brainres.2025.149663","DOIUrl":"10.1016/j.brainres.2025.149663","url":null,"abstract":"<div><div>In Parkinson’s disease (PD), the disturbance of energy metabolism due to glucose metabolic reprogramming may be a critical factor contributing to neuronal degeneration and death. Glycolysis, as the core process of glucose metabolism, not only serves as a fundamental source of energy but also integrates various metabolic pathways. However, the precise role of alterations in glycolysis-related pathways in the progression of PD remains elusive. We compared and analysed datasets from human databases of patients with PD and healthy controls to identify differentially expressed genes associated with glycolysis. Using the least absolute shrinkage and selection operator regression method and multivariate logistic regression analysis, we identified glucan-branching enzyme 1 (GBE1) as the most confident glycolytic gene implicated in PD. We validated the low expression of GBE1 in 1 − methyl − 4 − phenyl − 1,2,3,6 – tetrahydropyridine (MPTP)-induced PD animal models. Stereotaxic injection-mediated overexpression of GBE1 in striatal neurons improved motor dysfunction in these animal models. In vitro experiments demonstrated that GBE1 promotes the expression of lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB), enhances cellular glycolytic flux, and thereby increases the viability of PC12 cells under MPP⁺ treatment. Additionally, GBE1 alleviates mitochondrial dysfunction and restores oxidative phosphorylation in PD. In summary, by integrating machine learning and bioinformatics approaches, we identified GBE1, a glycolysis-related gene with significant implications for PD, elucidating its crucial role in glucose metabolic reprogramming and identifying potential therapeutic targets for modulating glucose metabolism in PD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1859 ","pages":"Article 149663"},"PeriodicalIF":2.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923637","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":"AMPK mediates the anti-ferroptosis effect of acupuncture in cerebral ischemia–reperfusion rats","authors":"Rong Wang ,&nbsp;Jun-feng Xu","doi":"10.1016/j.brainres.2025.149662","DOIUrl":"10.1016/j.brainres.2025.149662","url":null,"abstract":"<div><h3>Background</h3><div>Acupuncture is clinically effective in the treatment of ischemic stroke. The report suggests that energy stress inhibits ferroptosis in part through AMPK. However, whether the effect of activating AMPK is related to ferroptosis in ischemic stroke and whether acupuncture can achieve neuroprotection against ischemic brain injury through the pathway of inhibiting ferroptosis by activating AMPK has not been confirmed.</div></div><div><h3>Methods</h3><div>In this experiment, all rats were randomly divided into 4 groups: Sham group, MCAO/R group, MA (MCAO/R + acupuncture) group, and MAM (MCAO/R + acupuncture + metformin) group. The middle cerebral artery occlusion/reperfusion injury (MCAO/R) model was created by the wire embolism method, and the MA and MAM groups received acupuncture treatment with electrotherapy (1 mA, 2/15 Hz, 20 min each), while the MAM group continued to receive metformin (oral gavage 200 mg/kg) after successful modelling. Neurological deficit score and infarct volume were measured, Prussian blue staining and mitochondrial structural changes were observed, and Fe2+ and MDA levels were determined in the brain tissue of the rats. Western blot results were analyzed to determine differences in the expression of TFR1, SLC7A11, GPX4 and AMPK、p-AMPK proteins in order to explore the possible pathological processes involved in cerebral ischemia at behavioral, histological and molecular levels and the possible protective mechanisms of acupuncture.</div></div><div><h3>Results</h3><div>Acupuncture attenuated ischemia–reperfusion-induced brain damage and mitochondrial damage. Further studies showed that acupuncture reduced the levels of Fe2+, MDA and the expression of TFR1 protein and increased the expression of SLC7A11 and GPX4 protein in the diseased hippocampal region of MCAO/R rats. In addition, metformin, as an AMPK activator, significantly enhanced the protective effect of acupuncture on cerebral ischemic injury and enhanced the acupuncture-mediated reduction of Fe2+, MDA levels and TFR1 protein expression and the increase of SLC7A11 and GPX4 protein expression in the lesioned hippocampal region of MCAO/R rats.</div></div><div><h3>Conclusions</h3><div>These findings suggest that acupuncture can inhibit ferroptosis and thus exert a protective effect against ischemic brain injury, and that this mechanism may be achieved by activating AMPK. This extends the mechanism of action of acupuncture in the treatment of ischemic stroke.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1860 ","pages":"Article 149662"},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901901","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":"Association between Electroencephalographic microstates abnormalities and cognitive dysfunction in drug-naive MDD","authors":"Qin Qin ,&nbsp;Xinyu Liu ,&nbsp;Bin Wang ,&nbsp;Xin Wang ,&nbsp;Sixiang Liang ,&nbsp;Chao Chen ,&nbsp;Meijia Li ,&nbsp;Chuanliang Han ,&nbsp;Xixi Zhao","doi":"10.1016/j.brainres.2025.149660","DOIUrl":"10.1016/j.brainres.2025.149660","url":null,"abstract":"<div><h3>Objectives</h3><div>This study aims to investigate the link between Electroencephalography (EEG) microstate anomalies and cognitive impairments in individuals with drug-naive Major depressive disorder (MDD).</div></div><div><h3>Methods</h3><div>We recruited 29 patients with drug-naive MDD and 30 healthy controls. The Hamilton Depression Rating Scale (HDRS-17) measured symptom severity, the MATRICS Consensus Cognitive Battery (MCCB) assessed neurocognitive function, and resting-state EEG data were collected using 64 scalp electrodes. Analysis of EEG microstates was conducted via the Microstate Analysis plugin for EEGLAB.</div></div><div><h3>Results</h3><div>MDD group had lower scores in six neurocognitive MCCB domains. For EEG microstates, four similar ones (A − D) were found in both groups. Notably, microstate C duration was lower in MDD group (t = 4.549, <em>P</em> &lt; 0.001), microstate D occurrence (t = 2.258, <em>P</em> = 0.028) and proportion (t = 3.733, <em>P</em> &lt; 0.001) were lower in MDD group. There were significant differences in all 4 microstate transition probabilities between groups. For example, A − B, B − A etc. transitions were higher in MDD, while A − C, A − D etc. were lower.<!--> <!-->The proportion of microstate D was found positively correlated with Speed of processing (SOP) score (r = 0.499, df = 26, <em>P</em> = 0.007) and Working memory (WM) score (r = 0.451, df = 26, <em>P</em> = 0.016). The Occurrence of microstate D was found positively correlated with SOP score (r = 0.383, df = 26, <em>P</em> = 0.044) and WM score (r = 0.389, df = 26, <em>P</em> = 0.041).</div></div><div><h3>Conclusions</h3><div>MDD patients show alterations in sub-second brain dynamics, characterized by a decreased proportion and occurrence of microstate D and shorter duration of microstate C, and significant shifts in microstate transition probabilities. These changes correlate with cognitive deficits across several domains, including processing speed and working memory.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1860 ","pages":"Article 149660"},"PeriodicalIF":2.7,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143911868","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 correlation between center of pressure and cerebral cortex activation characteristics in patients with stroke: A functional near-infrared spectroscopy study","authors":"Jue Liu ,&nbsp;Yifei Xia ,&nbsp;Qun Zhang ,&nbsp;Xinwei Tang ,&nbsp;Ruiping Hu ,&nbsp;Yulian Zhu","doi":"10.1016/j.brainres.2025.149648","DOIUrl":"10.1016/j.brainres.2025.149648","url":null,"abstract":"<div><div>Balance impairment is common among patients with hemiplegia after stroke, yet the relationship between standing balance and cerebral cortex activation under eyes-open and eyes-closed conditions remains unclear. This study aims to explore these correlations to guide targeted neural regulation. Thirty-one stroke patients from Huashan Hospital, Fudan University (2021–2022), were assessed for the sway of center of pressure (COP) under the aforementioned conditions. Brain activation coefficient <em>β</em> value was measured using functional near-infrared spectroscopy (fNIRS). Pearson’s correlation analysis showed that during standing with eyes open, the right pre-motor cortex (PMC) and supplementary motor area (SMA) was moderately correlated with short-time dispersion degree of the COP movement area (r = 0.56, <em>P</em> = 0.001), long-time dispersion of the COP velocity (r = 0.57, <em>P</em> &lt; 0.001), medial–lateral-acceleration of the COP (r = 0.63, <em>P</em> &lt; 0.001), medial–lateral-speed of the COP (r = 0.63, <em>P</em> &lt; 0.001), and the Score (r = 0.56, <em>P</em> = 0.001). Significant correlations with medial–lateral-speed of the COP were also found in the bilateral PMC, SMA, the left prefrontal eye movement and the left primary motor cortex (r = 0.48–0.56, all <em>P</em> &lt; 0.01). Paired-samples t-tests showed significant differences in almost all COP variables between eyes-open and eyes-closed conditions (<em>P</em> &lt; 0.05), but no significant differences in in the mean cerebral cortex activation across all channels. Our findings indicate that the channel with the strongest representation of the motor area of the affected hemisphere may be an important regulatory target for balance disorders.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1860 ","pages":"Article 149648"},"PeriodicalIF":2.7,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904525","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":"NRXN3-NLGN1 complex influences the development of depression induced by maternal separation in rats","authors":"Yuru Rong ,&nbsp;Wanyue Yan ,&nbsp;Zheng Gao ,&nbsp;Yujing Yang ,&nbsp;Chengyun Xu ,&nbsp;Caiyi Zhang","doi":"10.1016/j.brainres.2025.149659","DOIUrl":"10.1016/j.brainres.2025.149659","url":null,"abstract":"<div><div>Early-life stress (ELS) increases the risk of major depressive disorder in children and adolescents. However, the molecular and cellular mechanisms of major depressive disorder (MDD) induced by ELS are poorly understood. Here, we establish a stress model in rats in which maternal separation stress (MS) during the postnatal period increases susceptibility to restraint stress (RS) later in life. In terms of mechanism, MS causes long-lasting synaptic plasticity alterations in rats, which is accompanied by reduced branch and spine lengths in the hippocampus. We identified the role of the cell adhesion factor neurexin 3 (NRXN3) and its ligand neuroligin 1 (NLGN1) as mediators of these effects. NRXN3 and NLGN1 downregulation in the hippocampus occurred prior to the observed synaptic changes and depression-related behaviors. In conclusion, NRXN3 is involved in the development of depression induced by maternal separation, and the specific mechanism involves the NRXN3-NLGN1 complex, which can mediate synaptic plasticity and increase susceptibility to<!--> <!-->depression.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1858 ","pages":"Article 149659"},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877183","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":"Systematic review of optimizing brain-targeted vitamin D delivery: Novel approaches to enhance mental illness therapeutics","authors":"Jinghu He ,&nbsp;Zhiyuan Gao ,&nbsp;Xilian Li ,&nbsp;Long Zhao ,&nbsp;Xue Tian ,&nbsp;Biao Gao","doi":"10.1016/j.brainres.2025.149656","DOIUrl":"10.1016/j.brainres.2025.149656","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D is increasingly recognized for its neuroprotective, anti-inflammatory, and immunomodulatory roles in mental health. However, its delivery to the central nervous system remains constrained by various factors.</div></div><div><h3>Objective</h3><div>This systematic review evaluates strategies for optimizing brain-targeted vitamin D delivery, highlighting molecular, physiological, and technological approaches to enhance its efficacy in mental disorders.</div></div><div><h3>Methods</h3><div>Following PRISMA guidelines, a comprehensive search across PubMed, Web of Science, Scopus, Embase, and PsycINFO was conducted. Relevant studies were assessed thematically, focusing on BBB transport mechanisms, nanocarriers, structural modifications, and transporter-mediated delivery.</div></div><div><h3>Results</h3><div>Strategies including nanotechnology, biotin-based transporter targeting (e.g., SMVT/SLC5A6), DBP–Megalin/Cubilin-mediated transcytosis, and intranasal administration show promise in enhancing vitamin D brain uptake. Differences between serum and brain vitamin D concentrations, genomic and non-genomic VDR pathways, and psychiatric disorder-specific associations (e.g., depression, schizophrenia, ASD) were also examined.</div></div><div><h3>Conclusions</h3><div>Although limited by the scarcity of large-scale clinical data, emerging strategies demonstrate significant potential in enhancing brain-targeted vitamin D delivery. These findings lay a foundation for future translational research aimed at precision mental health interventions.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1858 ","pages":"Article 149656"},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877184","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":"Early body representation EEG signals in cervical vs. thoracic spinal cord injuries with neuropathic pain","authors":"Scott Ian Frank ,&nbsp;Ramanamurthy V. Mylavarapu ,&nbsp;Eva Widerstrom-Noga ,&nbsp;Roberta Vastano","doi":"10.1016/j.brainres.2025.149658","DOIUrl":"10.1016/j.brainres.2025.149658","url":null,"abstract":"<div><div>Spinal cord injury (SCI) not only causes severe sensorimotor impairments but also leads to disruptions in body representation, including body schema. While the neurological differences between cervical and thoracic injuries are well established, the impact of the level of injury on body schema is less understood. Deeper insights into how change in body schema is affected by injury severity may further individual rehabilitation strategies and outcomes for individuals with SCI. This study explores event-related potentials (ERPs) between individuals with cervical and thoracic injuries in response to body-related and non-body-related stimuli presented in two rotation angles (easy: 75° and difficult: 150°) while completing a laterality judgment task. Individuals with cervical injury showed reduced amplitudes of posterior P100 and anterior N100 compared to the thoracic group only when the body-related stimuli were presented in a difficult rotation angle. We discuss that the variations in early modulation of ERPs can be attributed to the underlying sensorimotor challenges associated with different levels of injury. This work enhances our understanding of cognitive processing in SCI populations to better inform rehabilitation strategies.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1858 ","pages":"Article 149658"},"PeriodicalIF":2.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143877185","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":"Peripheral lymphocyte counts and regional cerebral blood flow on brain SPECT correlate in Alzheimer’s disease: A retrospective cross-sectional study","authors":"Hidehito Miyazaki ,&nbsp;Keiko Ide ,&nbsp;Hiroyuki Yamaguchi ,&nbsp;Matsuyoshi Ogawa ,&nbsp;Naoya Aoki ,&nbsp;Omi Katsuse ,&nbsp;Toshinari Odawara ,&nbsp;Takeshi Asami","doi":"10.1016/j.brainres.2025.149657","DOIUrl":"10.1016/j.brainres.2025.149657","url":null,"abstract":"<div><h3>Background</h3><div>Given emerging evidence of immune involvement in Alzheimer’s disease (AD), we aimed to clarify whether peripheral lymphocyte counts are associated with regional cerebral blood flow (rCBF) as measured by brain single-photon emission computed tomography (SPECT). Identifying such a relationship may help to establish early, accessible biomarkers of disease progression.</div></div><div><h3>Methods</h3><div>Participants were 111 patients diagnosed with AD at the Yokohama City University Hospital Medical Center for Dementia Diseases between January 2021 and December 2023 and who underwent blood tests and brain SPECT. Sex, age, cognitive function tests, peripheral blood values, and rCBF on brain SPECT were investigated retrospectively. Neutrophil and lymphocyte counts were extracted from blood values. In addition, the rCBF in each region (frontal, parietal, temporal, occipital, and limbic system) was calculated from brain SPECT, and correlation analysis between lymphocytes and rCBF was performed.</div></div><div><h3>Results</h3><div>Significant positive correlations between lymphocyte counts in peripheral blood and rCBF were found in all regions except the left frontal lobe. In particular, the correlation coefficient between rCBF and lymphocyte count was highest in the right temporal lobe (ρ = 0.311, <em>P</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>Peripheral blood lymphocyte counts are positively related to rCBF on brain SPECT, and lymphocytes can be an early biomarker that can be tested inexpensively and easily. Limitations include the retrospective cross-sectional design and single-center setting, which preclude analysis of causality and changes over time.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1859 ","pages":"Article 149657"},"PeriodicalIF":2.7,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876935","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}