Current Neuropharmacology最新文献

{"title":"Sex-specific Associations between Immune Parameters and Clinical Symptoms in First-episode Patients with Schizophrenia.","authors":"Anle Pan, Meihong Xiu, Jiahong Liu, Jing Yao, Yuanyuan Huang","doi":"10.2174/011570159X354419250217100855","DOIUrl":"https://doi.org/10.2174/011570159X354419250217100855","url":null,"abstract":"<p><strong>Introduction: </strong>Inflammation is linked to the pathophysiology of schizophrenia. The neutrophil- to-lymphocyte ratio (NLR), a measure of systemic inflammation, has been reported to be associated with schizophrenia. However, few studies have examined the sex-specific association between neutrophil-to-lymphocyte ratio (NLR) and clinical symptoms in schizophrenia. This study aimed to explore sex differences in NLR and its correlation with symptoms in first-episode schizophrenia (FES) patients.</p><p><strong>Method: </strong>Ninety-seven FES patients and 65 control subjects were recruited. The severity of clinical symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS), and white blood cells were calculated. We performed a cross-sectional analysis comparing NLR in males and females in the patient and control groups. We explored its sex-specific associations with clinical symptoms in the patient group.</p><p><strong>Results: </strong>We found that neutrophil (NEU) counts and NLR were higher in male patients compared to female patients with schizophrenia. There were no significant differences in white blood cell counts and NLR in healthy controls. Linear regression analysis showed that NEU counts were associated with clinical symptoms in male patients, and NLR correlated with symptoms in female patients after controlling for age, onset age, and years of education.</p><p><strong>Conclusion: </strong>Our study suggests that NLR values and NEU counts were higher in male patients compared with female patients with schizophrenia and that the association between NLR or NEU and clinical symptoms was sex-specific.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dual Role of Microglia in Multiple Sclerosis and its Implications for Diagnostics and Repair.","authors":"Melissa T Goulart, Davi T U Queiroz, Fabíola M Ribeiro","doi":"10.2174/011570159X352356241126044933","DOIUrl":"https://doi.org/10.2174/011570159X352356241126044933","url":null,"abstract":"<p><p>Microglia play a crucial role in the development, immune surveillance, and repair of the central nervous system. These cells play a multifaceted role in multiple sclerosis (MS), with evidence suggesting that microglia can promote both active inflammation and remyelination. For instance, it has been shown that microglia can support the development of oligodendrocytes and phagocytose myelin debris, thus aiding in proper remyelination. However, microglia overactivation in MS lesions exacerbates neuroinflammation by releasing inflammatory cytokines and facilitating the activation of astrocytes and immune cells, promoting demyelination and, ultimately, driving MS pathology. In fact, it has been shown that there is a correlation between activated microglia patterns and the chronicity of MS. Thus, although it is difficult to be certain whether these cells are friends or foes, there is no doubt that microglia will be a relevant target for MS diagnosis and treatment in the future, when further research will help to clarify the role of these cells in MS. MRI and PET scan allow evaluation of microglia/macrophages biomarkers, facilitating the clinical assessment of a patient's disease stage. Moreover, new microglia-specific markers are being discovered, which will increase diagnostic precision, helping to identify active and chronic MS lesions. Because microglia are involved are in all MS phases, these cells are also an important drug target. In this review, we focus on the current understanding of the role of microglia in MS progression as well as on the evidence supporting both inflammatory and reparative functions of these cells. We will also review how microglia may yield new biomarkers for MS diagnosis and serve as a potential target for therapy.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Inflammation Profile of Cerebellar Ataxia.","authors":"Cuiling Tang, Qi Deng, Xinrong Yuan, Ziyan Ding, Jian Hu, Linliu Peng, Hongyu Yuan, Na Wan, Yiqing Gong, Siyu Ding, Yan Tan, Lijing Lei, Linlin Wan, Rong Qiu, Beisha Tang, Zhao Chen, Hong Jiang","doi":"10.2174/011570159X379620250225075810","DOIUrl":"https://doi.org/10.2174/011570159X379620250225075810","url":null,"abstract":"<p><strong>Objectives: </strong>The objective of this study is to determine the characteristics of peripheral inflammatory profiles and their correlations with the clinical features in patients with cerebellar ataxia.</p><p><strong>Methods: </strong>We conducted a cross-sectional study on a cohort of 140 cerebellar ataxia patients, including 74 patients with spinocerebellar ataxia (SCA), 66 patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C), and 145 healthy controls (HCs). Inflammatory profiles (PLT, MPV, NLR, PLR, MLR, SII, AISI and ESR) were measured in peripheral blood, and were compared by ANOVA and Kruskal-Wallis test. The receiver operating characteristic (ROC) curve and the area under curve (AUC) were performed to determine the sensitivity and specificity of the inflammatory markers. Spearman correlation and partial correlation analysis were performed to detect the association between inflammatory profiles and clinical scales in cerebellar ataxia.</p><p><strong>Results: </strong>Inflammatory profiles from peripheral blood showed significant difference between different groups. Significant variations were observed in MPV, NLR, MLR, SII, AISI and ESR between cerebellar ataxia and HCs groups (p<0.05). NLR and ESR in both SCA and MSA-C groups were increased compared with HCs (p<0.05). The difference of MHR between SCA and MSA-C groups was observed based on HDL variation (p<0.05). The combination of ESR and PLT distinguished SCA from MSA-C (AUC=0.800). In addition, MLR was significantly corelated with clinical scales, including SARA and ICARS in SCA group as well as UMSARS and FAB in MSA-C group (r>0.3/r<-0.3).</p><p><strong>Conclusion: </strong>Significant variation in peripheral inflammatory profiles was firstly identified in Chinese genetic ataxias and non-genetic cerebellar ataxia cohort, which showed the potential clinical correlations between peripheral inflammatory phenotype and severity of ataxia.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances and Challenges in Traumatic Brain Injury from a Forensic Perspective.","authors":"Shu-Quan Zhao, Yan-Wei Shi, Xiao-Guang Wang, Ke Liu, Hu Zhao","doi":"10.2174/011570159X352125241031030110","DOIUrl":"https://doi.org/10.2174/011570159X352125241031030110","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) is one of the leading causes of death and disability. Animal and clinical studies of TBI have greatly changed the clinical practice of TBI with the development and application of new technologies. However, with the development of forensic science, legal issues related to TBI continue to emerge, and it is still far from satisfactory that the practical application of relevant research findings as legal evidence in court practice. This review discusses an overview of the latest progress of TBI through neuropathological changes, secondary injury mechanisms, postmortem neuroimaging, cognitive, emotional, and behavioral impairments, biomarkers, and the effects of toxins and drugs on brain injury from a forensic perspective. Meanwhile, we highlight the interpretability and limitations of findings on TBI in legal proceedings are ongoing challenges.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of Microglia in Synaptogenesis, Synaptic Pruning, and Synaptic Plasticity in Physiological Conditions and Central Nervous System Disorders.","authors":"Meizhen Xie, Tian Wang, Jiachun Feng, Di Ma, Liangshu Feng, Yulei Hao","doi":"10.2174/1570159X23666250225091729","DOIUrl":"https://doi.org/10.2174/1570159X23666250225091729","url":null,"abstract":"<p><p>Microglia are resident immune cells in the brain that have been widely studied for their immune surveillance and phagocytosis. In recent years, the important role of microglia in synapse formation, elimination, and plasticity is gradually being recognized. Synapses are the main communication mode between neurons. They undergo constant changes in quantity and plasticity throughout the life cycle, which is the basis of learning and memory. Microglia are highly motile, branched forms that monitor the microenvironment of the central nervous system (CNS) and promote synapse formation and maturation. They recognize and phagocytose redundant synapses through specific phagocytosis receptors. Furthermore, microglia regulate synaptic plasticity by releasing various effectors. The roles of microglia on synapses ensure the proper function of neural networks. Synaptic dysfunction and microglia activation are common features in CNS disorders, such as Alzheimer's disease, Parkinson's disease, ischemic stroke, cerebral hemorrhage, traumatic brain injury, multiple sclerosis, and epilepsy. Highly heterogeneous microglia exhibit diverse functions in these diseases and participate in disease progression by exacerbating or inhibiting synaptic dysfunction, in addition to neuroimmune and inflammation. In this article, we summarize the role of microglia on synapses under physiological conditions and in CNS disorders. We highlight the possible mechanisms by which microglia regulate synapse function in CNS disorders and how this affects the progression of the diseases. We aim to explore potential therapeutic targets for CNS disorders.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ISR Modulators in Neurological Diseases.","authors":"Alexander Pavlovich Kalinin, Ekaterina Sergeevna Zubkova, Mikhail Yuryevich Menshikov, Yelena Victorovna Parfyonova","doi":"10.2174/011570159X361653250213114821","DOIUrl":"https://doi.org/10.2174/011570159X361653250213114821","url":null,"abstract":"<p><p>The dysfunction of different cells lies in the pathogenesis of neurological diseases and is usually associated with cellular stress. Various stressors trigger the integrated stress response (ISR) signaling, whose highly conserved mechanism is primarily aimed at protecting a stress-exposed cell to cope as safely as possible with such stressful conditions. On the contrary, if a cell is unable to cope with excessive stress, the ISR can induce apoptosis. The ISR mechanism, whose main stage is the inhibition of translation machinery in favor of the synthesis of specific proteins, including the transcription factors ATF3, ATF4, CEBPA, and CEBPB, which function only as dimers and determine the uniqueness of the ISR response in each individual case, thus ensures different outcomes of the ISR. Inhibition of global protein synthesis is achieved through phosphorylation of eIF2α by PERK, HRI, PKR, or GCN2. To date, a number of compounds have been developed that modulate the ISR, including activators and inhibitors of the abovementioned ISR kinases as well as modulators of p-eIF2α dephosphorylation. They target different ISR stages, allowing a broad ISR modulation strategy. At the same time, there are no drugs that are both exceptionally safe and effective for the treatment of several neurological diseases, so there is an urgent need for new approaches to the treatment of these disorders. In this review, we represent ISR signaling as an important participant in the pathogenesis of neurological diseases. We also describe how various ISR modulators may become a part of future therapies for these diseases.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beneficial and Detrimental Effects of Uric Acid on Alzheimer's Disease.","authors":"O V Tovchiga, I Inkielewicz-Stepniak","doi":"10.2174/011570159X349365250128072146","DOIUrl":"https://doi.org/10.2174/011570159X349365250128072146","url":null,"abstract":"<p><p>The interconnection between brain function and hyperuricemia remains controversial since the available evidence indicates both the potent neuroprotective role of uric and its negative cardiovascular and metabolic effects, possible prooxidant activity. A mixed (protective and risk) effect of uric acid on neurological disorders was assumed. Among the neurodegenerative diseases, Alzheimer's disease remains the most prevalent, causes disability, and lacks highly effective treatments. Therefore, this review aims to delineate the beneficial and detrimental effects of uric acid on Alzheimer's disease. This can not only facilitate estimating the benefits and risks of urate-lowering or urate-increasing interventions in different conditions but also can enhance understanding of the molecular pathways associated with the protective role of uric acid, leading to the identification of new therapeutic targets for neuroprotection. Firstly, we addressed interconnections between UA and AD in different patients and population subgroups. Secondly, we analysed which differences can arise at the level of uric acid transport to the brain, its influence on BBB, and its presence in brain tissue and cerebrospinal fluid. Such aspects as xanthine oxidase interrelationship with the risk of cognitive impairment was elucidated, as well as the unexpected interconnection between uric acid exchange and the cholinergic system. Finally, an analysis was done of the beneficial and detrimental effects of uric acid on such targets of Alzheimer's disease pathogenesis as the amyloid-β pathway, proinflammatory markers, peroxynitrite scavenging, and other aspects of prooxidant-antioxidant status.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Modulatory Effects of Anesthetics and Analgesics on Neurophysiological Monitoring and Underlying Mechanisms.","authors":"Yu Leng, Yi Teng, Jin Liu, Xian Zou, Mengchan Ou, Tao Zhu, Peng Liang, Cheng Zhou","doi":"10.2174/011570159X349119250127104107","DOIUrl":"https://doi.org/10.2174/011570159X349119250127104107","url":null,"abstract":"<p><p>Intraoperative Neurophysiological Monitoring (IONM) is an indispensable surgical tool that offers invaluable insights into neurological function across a spectrum of anatomical areas. By comprehensively assessing the integrity of the brain, brainstem, spinal cord, cranial nerves, and peripheral nerves, IONM plays a pivotal role in guiding surgical decision-making and optimizing patient outcomes, particularly in the context of high-risk procedures. Intraoperative drugs, especially anesthetics and/or analgesics, differentially modulate neurophysiological monitoring, which remarkably affects the application of neurophysiological monitoring under specific conditions and indicates the neurobiological mechanisms of anesthetics/analgesics. This review will describe various neurophysiological modalities utilized in intraoperative procedures, each employing a wide variety of physiological principles; summarize the modulatory effects of anesthetics/analgesics on these neurophysiological monitoring parameters; and elucidate their underlying mechanisms, with a particular emphasis on evoked potentials. Insights gleaned from this review can inform strategies of anesthesia management for surgeries that require IONM and guide future investigations on the mechanisms of anesthesia/analgesia.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a Rosiridin against Rotenone-induced Rats' Model of Parkinson's Disease: In-vivo Study and in silico Molecular Modeling.","authors":"Misbahuddin Rafeeq, Fahad A Al-Abbasi, Muhammad Afzal, Khalid Saad Alharbi, Ehssan Moglad, Salwa D Al-Qahtani, Hussam A Bukhari, Faisal Imam, Nadeem Sayyed, Imran Kazmi","doi":"10.2174/011570159X349553250126050134","DOIUrl":"10.2174/011570159X349553250126050134","url":null,"abstract":"<p><strong>Aim: </strong>The investigation aimed to study the outcome of rosiridin in Parkinson's disease (PD) induced by rotenone (ROT) in rodents.</p><p><strong>Methods: </strong>Rodents were randomized into IV groups and were induced with ROT followed by treatment with rosiridin. Group I-IV received saline as a vehicle, II-ROT (0.5 mg/kg S.C) for 28 consecutive days, III and IV- rosiridin 10 and 20 mg/kg orally with ROT. On completion of the experimental duration, behavioral investigations were carried out. Biochemical variables such as acetylcholinesterase (AChE), oxidative stress and antioxidants markers (Malondialdehyde-MDA, glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), anti-inflammatory (Interleukin-1 beta-IL-1β, IL-6, and tumor necrosis factor alpha-TNF-α), alteration in neurotransmitters (Serotonin-5-HT), norepinephrine, and dopamine-DA, along with metabolites such as 5-hydroxy indole acetic acid-5- HIAA),), mitochondrial complex I, II, IV, and caspase-3 activity were evaluated at the end of the experiment. Furthermore, molecular docking and dynamics were performed for target ligands.</p><p><strong>Results: </strong>Rosiridin significantly restored the level of AChE, oxidative stress and antioxidants markers (MDA, GSH, SOD, and CAT), anti-inflammatory (IL-1β, IL-6, and TNF-α), alteration in neurotransmitters, mitochondrial complex I, II, IV, and caspase-3 activity. Rosiridin has a favorable negative binding affinity to AChE (-8.99 kcal/mol). The results of the molecular dynamics simulations indicate that proteins undergo a substantial change in conformational dynamics when binding to rosiridin.</p><p><strong>Conclusion: </strong>In this study, rosiridin may exhibit neuroprotective properties against the Parkinson's model for treating PD.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Epigenetics in the Pathogenesis and Potential Treatment of Obsessive-compulsive Disorder.","authors":"Jacob Peedicayil","doi":"10.2174/011570159X347479241024120728","DOIUrl":"https://doi.org/10.2174/011570159X347479241024120728","url":null,"abstract":"<p><p>Obsessive-compulsive disorder is a common neuropsychiatric disorder that markedly affects the quality of life of affected patients. There is increasing evidence that abnormal epigenetic mechanisms of gene expression are involved in the pathogenesis of this disorder. This article reviews the available data on epigenetic abnormalities found in patients with this disorder. The article also reviews the data on the use of epigenetic therapy in the treatment of obsessive-compulsive disorder, and epigenetic changes noted during psychotherapy of patients with this disorder. More detailed knowledge of the role of abnormal epigenetic mechanisms underlying obsessive-compulsive disorder could facilitate the development of new drugs for treating this disorder and the development of biomarkers for this disorder.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}