Neuroprotection最新文献

{"title":"The role of angiotensin II type 1 receptor pathway in cerebral ischemia‒reperfusion injury: Implications for the neuroprotective effect of ARBs","authors":"Shuhan Huang, Meng Zhang","doi":"10.1002/nep3.45","DOIUrl":"https://doi.org/10.1002/nep3.45","url":null,"abstract":"Cerebral ischemia–reperfusion (I/R) injury is a crucial factor that impacts the prognosis of recanalization therapy for acute ischemic stroke (AIS). It has been found that the brain renin–angiotensin system, especially the angiotensin II type 1 receptor (AT1R) pathway, plays a significant role in cerebral I/R injury. This pathway is involved in processes such as oxidative stress, neuroinflammation, apoptosis, and it affects cerebrovascular autoregulation and the maintenance of blood–brain barrier. AT1R blocker (ARB), widely used as an antihypertensive agent, has demonstrated stroke prevention capabilities in numerous prospective studies, independent of its antihypertensive characteristics. Studies focusing on neurological diseases like Alzheimer's disease, Parkinson's disease, and cognitive impairment have confirmed that ARBs exhibit neuroprotective effects and aid in improving neurological functions. Preclinical studies have shown that ARBs can reduce infarct volume and brain edema, inhibit multiple signaling pathways associated with I/R injury, restore energy levels in damaged brain regions, and rescue the penumbra by promoting neovascularization in cerebral I/R models. These findings suggest that ARBs have potential to become a novel category of neuroprotecting agents for clinical treatment of AIS. Therefore, this review primarily provides a theoretical foundation and practical evidence for the future clinical utilization of ARBs as neuroprotective agents following reperfusion therapy for AIS. It outlines the role of cerebral I/R injury through the AT1R pathway and highlights the research progress made on ARBs in I/R models.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"205 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141387303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamate and excitotoxicity in central nervous system disorders: ionotropic glutamate receptors as a target for neuroprotection","authors":"Jorge Y. Magdaleno Roman, C. Chapa González","doi":"10.1002/nep3.46","DOIUrl":"https://doi.org/10.1002/nep3.46","url":null,"abstract":"Recent advances in neuroscience have illuminated the central role of glutamate dysregulation in various neurological disorders. The glutamatergic system has emerged as a central player in the pathophysiology of various neurological disorders. The dysregulation of glutamate signaling, leading to excitotoxicity and neuronal cell death, has been a focal point in understanding the underlying mechanisms of these conditions. This has prompted a paradigm shift in neuroprotection research, with a growing emphasis on targeting ionotropic glutamate receptors (iGluRs) to restore glutamatergic homeostasis. This review provides a comprehensive overview of recent advancements in the field of iGluR‐targeted neuroprotection. We further investigate the implications of glutamate dysregulation in the central nervous system (CNS) disorders, highlighting the complex interplay between excitotoxicity and neuroprotection. We elucidate the multifaceted factors that render neurons vulnerable to excitotoxic damage, emphasizing the need for innovative therapeutic approaches. This review provides an extensive survey of the burgeoning field of iGluR‐targeted neuroprotection. It showcases the significant potential of a wide array of compounds, encompassing both natural and synthetic agents, to modulate iGluRs and ameliorate excitotoxicity and oxidative stress‐induced neuronal damage. These compounds have demonstrated impressive neuroprotective effects in diverse experimental models, from glutamate‐induced toxicity to traumatic brain injuries. We advocate for further research and clinical investigations to harness the full therapeutic potential of iGluR modulation, heralding a promising era in neuroprotection and CNS disorder management.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"61 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141387461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel therapeutic strategies and common mechanisms of neurodegenerative diseases","authors":"Š. Lehtonen, Jukka Jolkkonen","doi":"10.1002/nep3.52","DOIUrl":"https://doi.org/10.1002/nep3.52","url":null,"abstract":"","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"100 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141387349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of gut microbiota in ischemic stroke: A narrative review of human and animal studies","authors":"Guangtang Chen, Xiaolin Du, Junshuan Cui, Jiaquan Song, Mingsong Xiong, Xi Zeng, Hua Yang, Kaya Xu","doi":"10.1002/nep3.44","DOIUrl":"https://doi.org/10.1002/nep3.44","url":null,"abstract":"The high incidence, mortality, and disability associated with ischemic stroke pose a significant threat to human health. The intestinal microbiota significantly influences the onset, progression, and prognosis of ischemic stroke. Gut flora plays a pivotal role in brain–gut interactions. The reflection of changes in the gut and brain caused by gut microbes facilitates the investigation of early warning biomarkers and potential therapeutic targets for ischemic stroke. In this narrative review of the relationship between gut microbiota and ischemic stroke, we primarily discuss three topics, grounded in real‐world human and animal studies. First, we examined the relationship between ischemic stroke and intestinal microbiota and its metabolites, delineate the overall characteristics of intestinal microbiota dysregulation in ischemic stroke, and assess the potential clinical value, prevailing research controversies, and unique phenomena of intestinal microbiota metabolites such as trimethylamine N‐oxide and short‐chain fatty acids in ischemic stroke. Second, we explored the potential communication pathways between intestinal flora and ischemic stroke based on the brain–gut axis, encompassing metabolic pathways, immune pathways, and neural pathways. Finally, we encapsulated the factors influencing the severity of ischemic stroke via intestinal flora, the pharmacological and nonpharmacological interventions that modulate intestinal flora in treating ischemic stroke, and the current research landscape of intestinal flora in the context of ischemic stroke sequelae.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"15 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140967101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting brain‐derived neurotrophic factor in the treatment of neurodegenerative diseases: A review","authors":"Dong Wang, Zhi‐Chen Lang, Shi-Nan Wei, Wei Wang, Hao Zhang","doi":"10.1002/nep3.43","DOIUrl":"https://doi.org/10.1002/nep3.43","url":null,"abstract":"Neurodegenerative diseases, marked by the gradual death of neurons, present a significant and growing public health challenge. Brain‐derived neurotrophic factor (BDNF) is crucial for the survival, development, and synaptic plasticity of neurons. Studies have consistently demonstrated that perturbed BDNF communication pathways are associated with the development and progression of neurodegenerative conditions, underscoring their potential as therapeutic targets. This review aimed to summarize the existing findings regarding BDNF expression, metabolism, and signaling transduction. Furthermore, we reviewed the intricate roles of BDNF signaling pathways in neurodegenerative diseases, elucidating their contributions to disease onset and progression. The latest advancements in targeting BDNF for the treatment of neurodegenerative diseases, including the development of small molecules, nucleic acid‐based therapeutics, and antibody‐based approaches, were also summarized. Despite recent strides, challenges persist, including a lack of comprehensive understanding of BDNF modulation across diverse neurodegenerative contexts and the absence of clinically approved BDNF‐targeted drugs.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"12 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141021112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research progress on intranasal treatment for Parkinson's disease","authors":"Puyuan Wen, Chao Ren","doi":"10.1002/nep3.42","DOIUrl":"https://doi.org/10.1002/nep3.42","url":null,"abstract":"Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder globally, significantly affecting the quality of life of affected individuals. Systemic drug delivery to the brain is inefficient because of first‐pass metabolism, the blood‐brain barrier (BBB), and the blood‐cerebrospinal fluid barrier. This inefficiency necessitates increased dosage as the disease progresses, leading to severe side effects that compromise the efficacy of the medication. Nose‐to‐brain (N2B) administration bypasses the BBB, allowing delivery of both small molecules and large protein substances to the central nervous system. Compared with systemic administration, this method enhances brain bioavailability, reduces enzymatic degradation, and minimizes systemic adverse reactions. However, the N2B delivery system is associated with several critical challenges, including mucociliary clearance, enzymatic degradation, and drug translocation via efflux mechanisms. This paper provides a comprehensive overview of the current research progress in intranasal treatment of PD, considering both preclinical and clinical studies, and discusses the physiological aspects and limitations of its delivery system.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"109 26","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140678821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond boundaries: Neuroprotective effects of steroids and ecdysteroids in SH‐SY5Y cells ‐ A systematic review","authors":"B. A. Tayeb, I. K. Njangiru, Renáta Minorics","doi":"10.1002/nep3.37","DOIUrl":"https://doi.org/10.1002/nep3.37","url":null,"abstract":"Steroids and ecdysteroids have been shown to exhibit a range of biological effects, including anti‐inflammatory, anticancer, and neuroprotective. This systematic review aims to highlight the evidence‐based neuroprotective and antioxidant effects of steroids and ecdysteroids in SH‐SY5Y neuroblastoma cells. A comprehensive literature search was conducted on May 11, 2023, without publication source restrictions, using various electronic databases, including PubMed, Web of Science (WoS), Scopus, and Cumulative Index to Nursing and Allied Health Literature. Of 103 articles, only 20 studies were included for investigating the neuroprotective effects of steroids and ecdysteroids in SH‐SY5Y cells exposed to oxidative stress or neurotoxic agents. The risk of bias and quality assessment of the included studies were evaluated in accordance with the Nature Publication Quality Improvement Project specific criteria. The selected studies reported the antioxidant effects of the tested compounds on SH‐SY5Y cells and demonstrated their ability to scavenge free radicals and prevent lipid peroxidation. These findings suggest that neurosteroids have potential therapeutic applications for the prevention and treatment of neurodegenerative diseases characterized by oxidative stress and neuronal damage. Some studies have investigated the molecular mechanisms underlying the neuroprotective and antioxidant effects of steroids and ecdysteroids in SH‐SY5Y cells. These mechanisms include the activation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, and the modulation of various signaling pathways, including the phosphoinositide 3‐kinase/protein kinase B and mitogen‐activated protein kinase/extracellular signal‐regulated kinase pathways. This review provides evidence that the tested compounds have remarkable neuroprotective and antioxidant effects in human neuroblastoma SH‐SY5Y cells.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"67 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140366284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating the impact of mechanisms causing neuronal degeneration","authors":"Xunming Ji, Piotr Walczak, Johannes Boltze","doi":"10.1002/nep3.41","DOIUrl":"https://doi.org/10.1002/nep3.41","url":null,"abstract":"","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"36 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140229052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of autoreactive Tc17 cells in the pathogenesis of experimental autoimmune encephalomyelitis","authors":"Yong Peng, Xiuli Zhang, Yandan Tang, Shunqing He, Guilan Rao, Quan Chen, Yahui Xue, Hong Jin, Shu Liu, Ziyang Zhou, Yun Xiang","doi":"10.1002/nep3.38","DOIUrl":"https://doi.org/10.1002/nep3.38","url":null,"abstract":"The pathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE—an animal model of MS) is primarily mediated by T cells. However, recent studies have only focused on interleukin (IL)‐17‐secreting CD4+ T‐helper cells, also known as Th17 cells. This study aimed to compare Th17 cells and IL‐17‐secreting CD8+ T‐cytotoxic cells (Tc17) in the context of MS/EAE.Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptides 35–55 (MOG35–55), pertussis toxin, and complete Freund's adjuvant to establish the EAE animal model. T cells were isolated from the spleen (12–14 days postimmunization). CD4+ and CD8+ T cells were purified using isolation kit and then differentiated into Th17 and Tc17, respectively, using MOG35–55 and IL‐23. The secretion levels of interferon‐γ (IFN‐γ) and IL‐17 were measured via enzyme‐linked immunosorbent assay using cultured CD4+ and CD8+ T cell supernatants. The pathogenicity of Tc17 and Th17 cells was assessed through adoptive transfer (tEAE), with the clinical course assessed using an EAE score (0–5). Hematoxylin and eosin as well as Luxol fast blue staining were used to examine the spinal cord. Purified CD8+ CD3+ and CD4+ CD3+ cells differentiated into Tc17 and Th17 cells, respectively, were stimulated with MOG35–55 peptide for proliferation assays.The results showed that Tc17 cells (15,951 ± 1985 vs. 55,709 ± 4196 cpm; p < 0.050) exhibited a weaker response to highest dose (20 μg/mL) MOG35–55 than Th17 cells. However, this response was not dependent on Th17 cells. After the 48 h stimulation, at the highest dose (20 μg/mL) of MOG35–55. Tc17 cells secreted lower levels of IFN‐γ (280.00 ± 15.00 vs. 556.67 ± 15.28 pg/mL, p < 0.050) and IL‐17 (102.67 ± 5.86 pg/mL vs. 288.33 ± 12.58 pg/mL; p < 0.050) than Th17 cells. Similar patterns were observed for IFN‐γ secretion at 96 and 144 h. Furthermore, Tc17 cell‐induced tEAE mice exhibited similar EAE scores to Th17 cell‐induced tEAE mice and also showed similar inflammation and demyelination.The degree of pathogenicity of Tc17 cells in EAE is lower than that of Th17 cells. Future investigation on different immune cells and EAE models is warranted to determine the mechanisms underlying MS.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140234891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 ischemic stroke and its modulation via extracellular vesicles and stem cells","authors":"Matteo Haupt, Stefan T Gerner, Thorsten R Doeppner","doi":"10.1002/nep3.39","DOIUrl":"https://doi.org/10.1002/nep3.39","url":null,"abstract":"Stem cell‐based therapies and extracellular vesicle (EV) treatment have demonstrated significant potential for neuroprotection against ischemic stroke. Although the neuroprotective mechanisms are not yet fully understood, targeting microglia is central to promoting neuroprotection. Microglia are the resident immune cells of the central nervous system. These cells are crucial in the pathogenesis of ischemic stroke. They respond rapidly to the site of injury by releasing pro‐inflammatory cytokines, phagocytizing dead cells and debris, and recruiting peripheral immune cells to the ischemic area. Although these responses are essential for clearing damage and initiating tissue repair, excessive or prolonged microglial activation can exacerbate brain injury, leading to secondary neuroinflammation and neurodegeneration. Moreover, microglia exhibit a dynamic range of activation states with the so‐called M1 pro‐inflammatory and M2 anti‐inflammatory phenotypes, representing the two ends of the spectrum. The delivery of both EVs and stem cells modulates microglial activation, suppressing pro‐inflammatory genes, influencing the expression of transcription factors, and altering receptor expression, ultimately contributing to neuroprotection. These findings underscore the importance of understanding the complex and dynamic role of microglia in the development of effective neuroprotective strategies to reduce the effects of ischemic stroke. In this review, we examine the current state of knowledge regarding the role of microglia in ischemic stroke, including their molecular and cellular mechanisms, activation states, and interactions with other cells. We also discuss the multifaceted contributions of microglia to stem cell‐ and EV‐based neuroprotection during an ischemic stroke to provide a comprehensive understanding of microglial functions and their potential implications in stroke therapies.","PeriodicalId":505813,"journal":{"name":"Neuroprotection","volume":"78 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140282288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}