Neuroprotection最新文献

{"title":"Recent advances in therapeutic strategies for Alzheimer's and Parkinson's disease using protein/peptide co-modified polymer nanoparticles.","authors":"Ramesha Hanumanthappa, Aravind Parthasarathy, Geetha B Heggannavar, Kiran Pc, Hemalatha Nanjaiah, Ramhari Kumbhar, Kuramkote Shivanna Devaraju","doi":"10.1002/nep3.60","DOIUrl":"10.1002/nep3.60","url":null,"abstract":"<p><p>The blood-brain barrier (BBB), which protects the brain from foreign molecules, makes delivery of drugs to the central nervous system is challenging. Nanoparticles (NPs) have been used over the past decade as drug delivery systems for the treatment of many disorders with great results. However, the effectiveness of NPs in delivering drugs to the brain for the treatment of Alzheimer's disease (AD) and Parkinson's disease (PD) is limited by the BBB. A recent breakthrough in nanotechnology delivery systems involves the use of surface-modified polymer NPs that enhance drug absorption and transport across the BBB; however, the technology still has some limitations. Studies conducted over the past few years have demonstrated that NPs modified with peptides or proteins can effectively cross the BBB via specific receptors, thus enhancing their delivery efficiency. In this review, we explore the use of polymer NPs combined with peptides and proteins for the treatment of AD and PD. This discussion focuses on the pathophysiology of these diseases, the BBB, and the potential of therapeutics based on co-modifying NPs with peptides and proteins. Additionally, we outline future directions for the use of polymer NPs conjugated with these biomolecules.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 4","pages":"255-275"},"PeriodicalIF":4.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rodent ischemic stroke models and their relevance in preclinical research.","authors":"Maria Thaysen, Emil Westi, Andrew N Clarkson, Petrine Wellendorph, Mie Kristensen","doi":"10.1002/nep3.62","DOIUrl":"10.1002/nep3.62","url":null,"abstract":"<p><p>Stroke is a leading cause of death and disability worldwide, with ischemic stroke caused by an occluded vessel accounting for the majority of cases. Current treatments are limited to recanalization, either through thrombectomy or thrombolysis. Approved pharmacological interventions to suppress stroke-associated excitotoxicity and neuroinflammatory events, leading to brain tissue death, are still lacking. Although numerous preclinical studies have been performed, they have yet to be translated into clinically relevant interventions. First-line preclinical in vivo studies include the use of rodent ischemic stroke models, which vary in terms of how well they replicate human stroke pathophysiology and phenotype (including the formation of blood clot, blood-brain barrier disruption, neuroinflammation, and edema generation). Thus, rodent ischemic stroke models must be carefully chosen according to the specific pharmacological intervention to be tested. In this review, we aimed to provide an overview of the five most commonly used rodent ischemic stroke models and critically assess their advantages and limitations, with a primary focus on the acute phases of stroke.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 4","pages":"296-309"},"PeriodicalIF":4.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel perspective in stroke neuroprotection: Leveraging hypoxic pocket insights for studying preconditioning and postconditioning.","authors":"Heng Zhao, Yan Meng, Sijie Li, Guiyou Liu, Xunming Ji","doi":"10.1002/nep3.61","DOIUrl":"10.1002/nep3.61","url":null,"abstract":"<p><p>This perspective article delineates the significant role of hypoxic pockets-localized, transient reductions in cerebral oxygenation-and their implications for stroke neuroprotection strategies. It posits that preconditioning and postconditioning, through interventions like isoflurane, exercise, remote limb ischemic conditioning, can mitigate these hypoxic pockets, potentially protecting the brain against ischemic events. These strategies exploit the brain's intrinsic adaptive capabilities to resist ischemic damage, underscoring a novel avenue for enhancing recovery and prevention efforts. The study emphasizes the need for further exploration into optimizing these interventions to harness their full potential in combating stroke's debilitating effects, marking a pivotal shift towards targeted neuroprotective measures focused on cerebral microenvironmental optimization.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 4","pages":"288-295"},"PeriodicalIF":4.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mass spectrometry-based proteomics for biomarker discovery in the <i>Drosophila</i> model of Parkinson's disease.","authors":"Mohammad Radid Khan, Ramisha A Rahman, Md Harunur Rashid, Md Shariful Islam","doi":"10.1002/nep3.59","DOIUrl":"10.1002/nep3.59","url":null,"abstract":"<p><p>Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide. Despite extensive research, the etiology of both familial and sporadic PD remains unclear. While most PD cases are sporadic, a significant minority are linked to genetic mutations, notably in the synuclein-alpha (<i>SNCA</i>) and leucine-rich repeat kinase 2 (<i>LRRK2</i>) genes. Animal models, such as <i>Drosophila melanogaster</i> (<i>D. melanogaster</i>), enable detailed study of these genetic mutations and their neurotoxic effects. Recent advancements in mass spectrometry-based proteomics have enhanced our understanding of PD by facilitating comprehensive analysis of protein expression and interactions in mutant and wild-type organisms, potentially revealing novel therapeutic targets. This review highlights the pivotal role of mass spectrometry-based proteomics in advancing PD research, emphasizing the contributions of <i>D. melanogaster</i> models in identifying potential biomarkers.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 4","pages":"276-287"},"PeriodicalIF":4.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood-based biomarkers of Alzheimer's disease: Standardization and comprehensiveness.","authors":"Ying Liu, Yu Guo, Jintai Yu","doi":"10.1002/nep3.58","DOIUrl":"10.1002/nep3.58","url":null,"abstract":"<p><p>Population aging is sweeping across the globe, resulting in a striking prevalence of Alzheimer's disease (AD) and dementia and a heavy economic burden. Given the time window of 10-20 years from pathological initiation to clinically detected cognitive impairment, early detection can significantly impact the prevention and control of AD. The invasiveness and high cost of cerebrospinal fluid biomarkers and positron emission tomography-computed tomography imaging limit large-scale disease screening. However, blood-based biomarkers (BBMs) lack these disadvantages, shedding light on their usefulness in the large-scale identification and prevention of AD. Prominent advancement has recently been made regarding BBMs of AD co-pathology (amyloid β, tau protein, neurofilament light polypeptide, and glial fibrillary acidic protein) to improve their accuracy as clinical diagnostics of AD to a level comparable to that of canonical methods, facilitating the large-scale clinical implementation of diagnostic tests with higher precision. To briefly summarize, the prospects of AD BBMs rely on standardization and comprehensiveness. Calibrating the sample collection procedure and clarifying the boundaries for indices and abnormalities are beneficial for constructing a canonical diagnostic assay. The comprehensive assembly of heterogeneous clinical evidence guarantees the accuracy of diagnosis and improves the workflow for early identification.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 4","pages":"246-254"},"PeriodicalIF":4.1,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of immunological processes and mild ambient atmosphere alterations on the brain in health and disease.","authors":"Piotr Walczak, Xunming Ji, Shen Li, Johannes Boltze","doi":"10.1002/nep3.57","DOIUrl":"10.1002/nep3.57","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" ","pages":"179-181"},"PeriodicalIF":4.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-6 induces cognitive impairment via toll-like receptor 4 (TLR4)-mediated neuroinflammation and neurodegeneration in mice with chronic kidney disease.","authors":"Yangping Shentu, Shuqing Ma, Simin Ye, Yaozhe Ying, Luhui Wang, Yun Zhu, YunTing Wang, Nan Jiang, Zongyuan Zhao, Chenfei Zheng, Chaosheng Chen, Yongheng Bai, Ying Zhou","doi":"10.1002/nep3.54","DOIUrl":"10.1002/nep3.54","url":null,"abstract":"<p><strong>Backgrounds: </strong>Past epidemiological and experimental studies in rodents have demonstrated that chronic kidney disease (CKD) leads to cognitive impairment. However, the underlying mechanism requires further investigation. Herein, a mouse model of CKD was established using conventional 5/6 nephrectomy. We aimed to examine the relationship between CKD and cognitive impairment and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>Cognitive behavior was assessed using the Morris water maze, novel object recognition test, and fear conditioning test. Further experiments were also conducted to investigate the underlying molecular mechanisms.</p><p><strong>Results: </strong>Our clinical data revealed a decrease in cognitive function among patients with CKD, accompanied by elevated plasma levels of pro-inflammatory cytokines. A positive correlation between cytokine concentrations and serum creatinine levels, as well as a significant positive correlation with cognitive dysfunction, were observed. Correlation analyzes demonstrated that hippocampal cytokine levels were positively correlated with serum creatinine levels and cognitive dysfunction in CKD model mice. Furthermore, 20 mg/mL interleukin-6 (IL-6) significantly decreased HT22 cell activity in vitro. Further, HT22 cells treated with IL-6 showed increased expression levels of toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88), thereby inducing the nuclear factor kappa-B p65 inflammatory pathway and mitochondria-dependent apoptosis. The CKD mouse model showed increased expression of TLR4 and cytokines in the hippocampus. <i>TLR4</i> knockdown antagonized the IL-6-mediated pro-inflammatory and pro-apoptotic effects in HT22 cells. <i>TLR4</i> knockdown in the CKD model mice decreased hippocampal inflammation and increased the number of neuron dendrites, thus ameliorated cognitive impairment.</p><p><strong>Conclusion: </strong>These results suggest that IL-6 triggers TLR4 activation to induce neuroinflammation and neurodegeneration in CKD, ultimately culminate in cognitive impairment.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 3","pages":"203-215"},"PeriodicalIF":4.1,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of neutrophil-to-lymphocyte ratio on the effect of hyperglycemia at admission on clinical outcomes after endovascular thrombectomy.","authors":"Tao Tang, Dawei Zhang, Fang Wang, Tieping Fan, Aline M Thomas, Xiaoyan Lan, Manhong Zhao, Di Li, Xinghui Zhao","doi":"10.1002/nep3.55","DOIUrl":"10.1002/nep3.55","url":null,"abstract":"<p><strong>Background: </strong>The neutrophil-to-lymphocyte ratio (NLR) is highly associated with stress responses to acute disorders and may be useful for differentiating hyperglycemia after stroke that is induced by stress or other causes. This study aims to evaluate whether the NLR modifies the effect of hyperglycemia at admission on clinical outcome after thrombectomy.</p><p><strong>Methods: </strong>We retrospectively enrolled 343 patients that underwent endovascular thrombectomy for acute anterior circulation large-vessel occlusion between January 2019 and June 2022. NLR at admission was used to dichotomize patients into low-NLR and high-NLR groups according to its median value. The primary outcome was 90-day functional independence (modified Rankin Scale Score 0-2). Secondary outcomes were 24 h symptomatic intracranial hemorrhage and 90-day mortality.</p><p><strong>Results: </strong>Overall, hyperglycemia at admission decreased the likelihood of functional independence (adjusted odds ratio [OR]: 0.34, 95% confidence interval [95% CI]: 0.19-0.60, <i>p</i> < 0.001). There was a significant interaction between the NLR and hyperglycemia at admission on functional independence (<i>p</i> = 0.024). Hyperglycemia at admission was negatively associated with functional independence in low-NLR patients (adjusted OR: 0.18, 95% CI: 0.07-0.42, <i>p</i> < 0.001), but not in high-NLR patients (adjusted OR: 0.67, 95% CI: 0.30-1.48, <i>p</i> = 0.320). Interactions between the NLR and hyperglycemia at admission on 24 h symptomatic intracerebral hemorrhage (<i>p</i> = 0.734) and 90-day mortality (<i>p</i> = 0.657) were not significant.</p><p><strong>Conclusions: </strong>The NLR modified the detrimental effect of hyperglycemia at admission on functional independence after thrombectomy. Low-NLR patients with hyperglycemia were at a high risk of poor outcomes, and might more likely benefit from aggressive glucose-lowering treatment.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 3","pages":"196-202"},"PeriodicalIF":4.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglial senescence in neurodegeneration: Insights, implications, and therapeutic opportunities.","authors":"Tobiloba Samuel Olajide, Toheeb O Oyerinde, Omolabake I Omotosho, Oritoke M Okeowo, Olayemi J Olajide, Omamuyouwi M Ijomone","doi":"10.1002/nep3.56","DOIUrl":"10.1002/nep3.56","url":null,"abstract":"<p><p>The existing literature on neurodegenerative diseases (NDDs) reveals a common pathological feature: the accumulation of misfolded proteins. However, the heterogeneity in disease onset mechanisms and the specific brain regions affected complicates the understanding of the diverse clinical manifestations of individual NDDs. Dementia, a hallmark symptom across various NDDs, serves as a multifaceted denominator, contributing to the clinical manifestations of these disorders. There is a compelling hypothesis that therapeutic strategies capable of mitigating misfolded protein accumulation and disrupting ongoing pathogenic processes may slow or even halt disease progression. Recent research has linked disease-associated microglia to their transition into a senescent state-characterized by irreversible cell cycle arrest-in aging populations and NDDs. Although senescent microglia are consistently observed in NDDs, few studies have utilized animal models to explore their role in disease pathology. Emerging evidence from experimental rat models suggests that disease-associated microglia exhibit characteristics of senescence, indicating that deeper exploration of microglial senescence could enhance our understanding of NDD pathogenesis and reveal novel therapeutic targets. This review underscores the importance of investigating microglial senescence and its potential contributions to the pathophysiology of NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Additionally, it highlights the potential of targeting microglial senescence through iron chelation and senolytic therapies as innovative approaches for treating age-related NDDs.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 3","pages":"182-195"},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11449118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five percent CO₂ inhalation alleviates hippocampal glutamate and water homeostasis disturbance, neuronal damage, and learning-memory impairment in sleep-deprived rats.","authors":"Zhihong Zhao, Xiaojun Zhang, Xiaolei Zhang, Shiyan Xie, Yue Chen, Lingfeng Lai, Lijing Xin, Jitian Guan, Yan Lin, Renhua Wu","doi":"10.1002/nep3.53","DOIUrl":"10.1002/nep3.53","url":null,"abstract":"<p><strong>Background: </strong>Sleep deprivation causes hippocampal injury, manifesting as neuronal damage and learning-memory impairment. These negative effects may be associated with disturbance of hippocampal glutamate and water homeostasis, which induces excessive neuronal excitability. Five percent CO₂ inhalation has been shown to suppress neuronal excitability. Here, we aimed to investigate whether 5% CO₂ inhalation facilitates the recovery of hippocampal glutamate and water homeostasis, neuron morphology, and learning-memory ability in sleep-deprived rats.</p><p><strong>Methods: </strong>Thirty-six Sprague-Dawley female rats were randomly divided into three groups including normal sleep (Group 1, NS, <i>n</i> = 12), sleep deprivation followed by sleep recovery (Group 2, SD+SR, <i>n</i> = 12), sleep deprivation followed by sleep recovery and 5% CO₂ inhalation (Group 3, SD+SR+CO₂, <i>n</i> = 12) by random number table. Each group was divided into two subgroups (<i>n</i> = 6 each subgroup) for different experiments randomly by random number table.</p><p><strong>Results: </strong>We found that 5% CO₂ inhalation facilitated the recovery of hippocampal glutamate concentration (7.549 ± 0.310, 8.716 ± 0.463, and 7.493 ± 0.281 mmol/L at Days 1, 3, and 5 in Group 3, F_2, 15 = 22.06, <i>p</i> < 0.0001) and hippocampal apparent diffusion coefficient mean value (8.210 ± 0.274, 7.685 ± 0.171, 8.265 ± 0.269 at Days 1, 3, and 5 in Group 3, F_2, 15 = 10.45, <i>p</i> = 0.0014), enhanced expression level of astrocyte-specific membrane protein glutamate transporter-1, promoted the polarized distribution of aquaporin 4, reduced hippocampal neuronal damage and improved learning-memory ability in sleep-deprived rats.</p><p><strong>Conclusion: </strong>This study showed that 5% CO₂ inhalation can serve as a novel strategy for alleviating sleep deprivation-induced hippocampal injury.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 3","pages":"216-227"},"PeriodicalIF":4.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}