Current Neuropharmacology - Online First
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Deciphering T Cell Dynamics in Alzheimer's Disease Pathogenesis: Insights and Implications
Authors: Qiqi Yang, Yunjie Qiu, Junjun Ni, Hui Li and Hong QingAvailable online: 21 March 2025More LessNeuroinflammation has emerged as a crucial factor in the pathogenesis of Alzheimer's disease (AD), paving the way for promising therapeutic interventions. Increasing evidence highlights the interplay between the peripheral immune system and the central nervous system (CNS) in driving neuroinflammation, with T lymphocytes playing a vital role in both regulatory and effector functions. Aberrant activation of T cells during the early stages of neuroinflammation perpetuates inflammatory responses by interacting with CNS glial cells and releasing pro-inflammatory mediators, such as IFN-γ, TNF-α, and IL-17. Studies have documented significant T cell activation and infiltration into the brain parenchyma in AD, contributing to disease progression. However, the specific mechanisms by which T cells mediate AD pathogenesis remain unclear. This comprehensive review synthesizes the current understanding of T cell involvement in AD pathology, emphasizing their aberrant activation, interactions with microglia, tau protein pathology, and the influence of gut microbiota. Finally, we propose potential treatment modalities for AD, highlighting the promise of T cell-based therapies currently under investigation in clinical trials. Understanding the critical role of T cells in intercellular communication and disease progression may enhance our comprehension of the pathophysiology of AD.
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Research Progress on Neural Cell Culture Systems
Authors: Ting Li, Xiaosong Qin and Qiang AoAvailable online: 12 March 2025More LessThe nervous system, including the central nervous system and peripheral nervous system, has the most intricate structure and function among all systems in the human body. In studies of physiological and pathological functions, cell culture systems serve as an indispensable tool to simulate the nervous system in vivo. Two-dimensional (2D), three-dimensional (3D), and four-dimensional (4D) neural cell culture systems are used to assess the functional interconnectivity of neuronal tissues and have markedly advanced in recent years. Although 2D culture systems have predominated, they cannot accurately recapitulate the dynamic complexity of the in vivo environment, cell-cell communication, and nervous system structures. Consequently, studies have shifted to using 3D or 4D cell culture systems to achieve more realistic biochemical and biomechanical microenvironments. Nevertheless, many limitations persist in 3D or 4D culture systems, including difficulties in deciphering dynamic and reciprocal remodeling processes, as well as the spatiotemporal distributions of oxygen, nutrients, and metabolic waste. Here, we review 2D, 3D, and 4D culture systems, discuss the advantages and limitations of these techniques in modeling physiologically and pathologically relevant processes, and suggest directions for future research.
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Advances and Challenges in Traumatic Brain Injury from a Forensic Perspective
Authors: Shu-Quan Zhao, Yan-Wei Shi, Xiao-Guang Wang, Ke Liu and Hu ZhaoAvailable online: 26 February 2025More LessTraumatic 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.
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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 and Cheng ZhouAvailable online: 18 February 2025More LessIntraoperative 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.
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Beneficial and Detrimental Effects of Uric Acid on Alzheimer’s Disease
Authors: O.V. Tovchiga and I. Inkielewicz-StepniakAvailable online: 18 February 2025More LessThe 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 (UA) 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 (AD). 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 blood-brain barrier (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.
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Withdrawn: Stable Gastric Pentadecapeptide BPC 157 as a Therapy of Severe Electrolyte Disturbances in Rats
Authors: Marija Medvidovic Grubisic, Sanja Strbe, Ivan Barisic, Dijana Balenovic, Vasilije Stambolija, Marin Lozic, Sanja Barsic Ostojic, Ivana Oreskovic, Helena Zizek, Klara Brcic, Luka Coric, Mario Staresinic, Vladimir Blagaic, Lidija Beketic Oreskovic, Zeljka Belosic Halle, Danijel Matek, Dragan Soldo, Boris Grizelj, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Predrag SikiricAvailable online: 24 January 2025More LessThe article has been withdrawn at the author's request from the website of the journal Current Neuropharmacology.
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Excessive Urinary p75ecd is a Potential Indicator of Amyotrophic Lateral Sclerosis: An American Cohort Study
Available online: 09 May 2024More LessIntroductionAmyotrophic lateral sclerosis (ALS) is an idiopathic, fatal, and rapidly progressive neurodegenerative disease. At present, neurofilament light (NFL) and phosphorylated neurofilament heavy (pNfH) proteins in biological fluids are commonly known prognostic biomarkers, but their levels stabilize over time. Thus, there is a critical gap in the field to identify unique biomarkers that can aid disease diagnosis, progression and monitoring the therapy response.
AimTo evaluate the presence of extracellular domain of p75 (p75ecd) in urine of ALS patients and healthy control volunteers in the North American cohort.
MethodAn enzyme-linked immunoassay (ELISA) and creatinine assay was used to determine the levels of p75ecd and creatinine in the urine of ALS patients and healthy control volunteers respectively. This assay demonstrated clear discrimination in the levels of the p75ecd in the urine samples of ALS patients as compared to healthy individuals.
ResultsIt was found that the concentration of p75ecd in ALS samples was significantly higher than that of healthy controls group. Additionally, high p75ecd levels were segregated with respect to age, sex, family history, occupation and drug treatment, medication status. Moreover, we observed differential expression patterns among the different stages of the disease. Our results followed the pattern that was observed in the Chinese, and Australian cohort.
ConclusionAltogether, our results indicate that the development of an efficient system for the detection of elevated levels of p75ecd in the urine could serve as a useful modality for early ALS diagnosis, disease progression, and monitoring the effectiveness of therapeutic interventions.
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