Neuroprotection最新文献

{"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":0.0,"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":"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":0.0,"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":"Tolerability and first hints for potential efficacy of motor‐cognitive training under inspiratory hypoxia in health and neuropsychiatric disorders: A translational viewpoint","authors":"Svea‐Solveig Mennen, Maren Franta, M. Begemann, Justus B. H. Wilke, Roman Schröder, Umer Javed Butt, Jonathan‐Alexis Cortés‐Silva, Umut Çakır, Marie Güra, Markus de Marées, Vinicius Daguano Gastaldi, J. Burtscher, Julie Schanz, Matthias Bohn, M. Burtscher, Andreas Fischer, Luise Poustka, Peter Hammermann, Markus Stadler, Fred Lühder, Manvendra Singh, K. Nave, K. Miskowiak, H. Ehrenreich","doi":"10.1002/nep3.47","DOIUrl":"https://doi.org/10.1002/nep3.47","url":null,"abstract":"Hypoxia is more and more perceived as pivotal physiological driving force, allowing cells in the brain and elsewhere to acclimate to lowered oxygen (O2), and abridged metabolism. The mediating transcription program is induced by inspiratory hypoxia but also by intensive motor‐cognitive tasks, provoking a relative decrease in O2 in relation to the acutely augmented requirement. We termed this fundamental, demand‐dependent drop in O2 availability “functional hypoxia.” Major players in the hypoxia response are hypoxia‐inducible factors (HIFs) and associated prolyl‐hydroxylases. HIFs are transcription factors, stabilized by low O2 accessibility, and control expression of a multitude of genes. Changes in oxygen, however, can also be sensed via other pathways, among them the thiol‐oxidase (2‐aminoethanethiol) dioxygenase. Considering the far‐reaching biological response to hypoxia, hitherto mostly observed in rodents, we initiated a translational project, combining mild to moderate inspiratory with functional hypoxia. We had identified this combination earlier to benefit motor‐cognitive attainment in mice. A total of 20 subjects were included: 13 healthy individuals and 7 patients with depression and/or autism spectrum disorder. Here, we show that motor‐cognitive training under inspiratory hypoxia (12% O2) for 3.5 h daily over 3 weeks is optimally tolerated. We present first signals of beneficial effects on general well‐being, cognitive performance, physical fitness and psychopathology. Erythropoietin in serum increases under hypoxia and flow cytometry analysis of blood reveals several immune cell types to be mildly modulated by hypoxia. To obtain reliable information regarding the “add‐on” value of inspiratory on top of functional hypoxia, induced by motor‐cognitive training, a single‐blind study—with versus without inspiratory hypoxia—is essential and outlined here.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"2 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266792","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":"Stress enhances expression of calcium‐binding proteins and NMDAR subunit genes in the rat hippocampus","authors":"Aravind Parthasarathy, Ramesha Hanumanthappa, Sarojini R. Bulbule, Kiran P.C., Hemalatha Nanjaiah, Gopinath G., Siddaiah B.M., David Muniswamy, Devaraju Kuramkote Shivanna","doi":"10.1002/nep3.35","DOIUrl":"https://doi.org/10.1002/nep3.35","url":null,"abstract":"Oxidative stress impairs the function of calcium‐binding proteins and deregulates calcium signaling in living organisms. We have previously explored the overexpression of calcium‐binding protein genes in a reactive oxygen and nitrogen species‐induced in vitro cell model of stress that leads to apoptosis. However, in in vivo models, low levels of stress leads to depressive‐like behavior. Here, we aimed to analyze gene expression of major calcium‐binding proteins (calcineurin, calmodulin, calsyntenin, synaptotagmin, and calreticulin) and N‐methyl‐d‐aspartic acid (NMDA) receptor subunits (glutamate receptor ionotropic [GluN] GluN1, GluN2A, and GluN2B) in the hippocampus of stress‐induced rats.Six‐week‐old male Wistar rats were assigned to two stress induction groups and a control group without stress (n = 6). Stress was induced by using H2O2 (3% in water) or by immobilization (using a sticky mat) over a period of 30 days. Expression of calcium‐binding protein genes in the hippocampus, antioxidant assays, structural alterations in hippocampal neurons, and depressive‐like behavior were determined.Expression of genes encoding calcium‐binding proteins calcineurin, calsyntenin, synaptotagmin and NMDA receptor subunit GluN1 was enhanced in both chemical and physical stress‐induced rats compared with control rats (4.25 ± 0.05 vs. 1.03 ± 0.02, p < 0.05, 2.05 ± 0.08 vs. 1.03 ± 0.02, p < 0.005; 2.2 ± 0.4 vs. 1.02 ± 0.03, p < 0.05, 1.98 ± 0.07 vs. 1.02 ± 0.03, p < 0.005; 1.4 ± 0.6 vs. 1.15 ± 0.09, p < 0.05, 1.39 ± 0.05 vs. 1.15 ± 0.09, p < 0.005), respectively. In stress‐induced rats, neurons in the CA2 region of the hippocampus were fewer and appeared disorganized compared with control rats. Furthermore, stress‐induced rats showed decreased mobility and lower sucrose preference in behavioral studies compared with control rats.Lower levels of reactive oxygen and nitrogen species (RONS) can also lead to stress in rats by affecting their calcium signaling, buffering capacity in the neurons leading to depressive symptoms.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"46 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141274035","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":"Neuroprotective effects of repetitive transcranial magnetic stimulation on Alzheimer's disease: Undetermined therapeutic protocols and mechanisms","authors":"Yang Zhu, L.M. Liao, Shihao Gao, Yong Tao, Hao Huang, Xiangqin Fang, Changyan Yuan, C. Gao","doi":"10.1002/nep3.40","DOIUrl":"https://doi.org/10.1002/nep3.40","url":null,"abstract":"Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by gradual deterioration of cognitive functions, for which an effective treatment is currently unavailable. Repetitive transcranial magnetic stimulation (rTMS), a well‐established noninvasive brain stimulation method, is utilized in clinical settings to address various neuropsychiatric conditions, such as depression, neuropathic pain, and poststroke dysfunction. Increasing evidence suggests that rTMS may enhance cognitive abilities in individuals with AD. However, its optimal therapeutic protocols and precise mechanisms are currently unknown, impeding its clinical implementation. In the present review, we aimed to summarize and discuss the efficacy‐related parameters in rTMS treatment, encompassing stimulus frequency, stimulus pattern, stimulus intensity, and the configuration of the stimulus coil. Furthermore, we reviewed promising rTMS therapeutic protocols involving various combinations of these factors, that were examined in clinical studies. Based on our analysis, we propose that a multisite high‐frequency rTMS (HF‐rTMS) regimen has value in AD therapy, and that promising single‐site protocols, such as HF‐rTMS, applied over the left dorsolateral prefrontal cortex, precuneus, or cerebellum are required to be validated in larger clinical studies. Lastly, we provide a comprehensive review of the potential mechanisms underlying the neuroprotective effects of rTMS on cognition in AD in terms of brain network modulation as well as cellular and molecular reactions. In conclusion, the interaction of diverse mechanisms may be responsible for the total therapeutic effect of rTMS on AD. This review provides theoretical and practical evidence for the future clinical application and scientific research of rTMS in AD.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"101 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140079934","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":"Exploring novel experimental treatments for major neurodegenerative disorders","authors":"Xunming Ji, Piotr Walczak, Johannes Boltze","doi":"10.1002/nep3.31","DOIUrl":"https://doi.org/10.1002/nep3.31","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"4 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138966425","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":"Activation of dopamine 2 receptors modulates glutamate decarboxylases 65 and 67 during stroke recovery in mice","authors":"D. Talhada, Robert Nilsson, Severin Walser, Georgios Michalettos, K. Ruscher","doi":"10.1002/nep3.28","DOIUrl":"https://doi.org/10.1002/nep3.28","url":null,"abstract":"Treatment with levodopa enhances recovery of lost neurological functions in preclinical stroke models and patients. Here, we studied whether dopamine signaling modulates GABAergic neurotransmission in parvalbumin‐positive interneurons after experimental stroke.Following block randomization, mice were subjected to experimental stroke induced by photothrombosis (PT). Two days after the insult, mice were treated either with the D1 receptor antagonist by R(+)‐SCH‐23390 (0.1 mg/kg), the selective D1 receptor agonist (R)‐(+)‐SKF‐38393 hydrochloride (1 mg/kg), the D2 receptor agonist R(−)‐2,10,11‐trihydroxy‐N‐propyl‐noraporphine hydrobromide hydrate (TNPA) (1 mg/kg), the D2 receptor antagonist S‐(−)‐eticlopride hydrochloride (0.3 mg/kg), or vehicle (saline) by daily intraperitoneal injection for five consecutive days, respectively. Recovery of function was assessed by paw placement and foot fault test before and on Days 2 and 7 after surgery.Mice treated with TNPA showed a statistically significant improvement of recovery compared to all other treatment conditions. Synthesis of gamma‐aminobutyric acid (GABA) was quantified by levels of full‐length and cleaved glutamate acid decarboxylase 67 and 65 (GAD65 and GAD67) in the peri‐infarct area and homotypic regions of the contralateral cortex. Compared to the other treatments, TNPA significantly reduced the level of the GAD67 isoform both in the ischemic and contralateral hemispheres. Levels of GAD65 were found significantly higher in the contralateral hemisphere in TNPA‐treated mice after PT accompanied by an increase in the 58 kDa‐truncated form.Our results point toward reduced GABA synthesis in a D2 receptor‐mediated mechanism possibly contributing to counteract functional inhibition after stroke.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139001845","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 potential of a combined cell‐based therapy and rehabilitation approach for stroke recovery","authors":"Abdulhameed Bakreen, Jukka Jolkkonen","doi":"10.1002/nep3.27","DOIUrl":"https://doi.org/10.1002/nep3.27","url":null,"abstract":"Activation of neuroprotective and particularly later neurorestorative mechanisms after stroke attempts to restore or compensate for lost functions. This potentially opens a wide window for restorative therapies to promote brain repair and improve long‐term functional recovery. Although extensively demonstrated in the preclinical setting, the efficacy of cell‐based therapies in stroke patients has been modest at best, if any at all. Translational failure may be due to the ineffective survival and integration of transplanted cells in pro‐death stroke microenvironments that are not conducive for the structural reconstruction of damaged brain tissue and repair‐related network reorganization. Optimal systemic delivery, timing, cell product, and dose remain open as well. Fortunately, a better understanding of the brain plasticity mechanisms underlying stroke recovery has ushered in a combination approach of cell‐based therapy and rehabilitation that is aimed at achieving additive, synergistic, or even maximal beneficial effects. This novel combination therapy is not only targeted at promoting exogenous and endogenous cell survival and augmenting stand‐alone restorative mechanisms but also at utilizing rehabilitation to facilitate a graft–host structural and functional integration and plasticity that would effectively remodel stroke tissue and restitute lost functions. This review presents an overview of the combination of cell‐based therapy and experimental rehabilitation in stroke models. It also discusses associated shortcomings as well as proposes strategies to address them and help facilitate the advancement of this combination approach.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"503 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138982927","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":"Neurological manifestations with jugular vein thrombosis linked to an inflammatory profile may be a sequela of long COVID","authors":"Elizabeth Mendoza‐Portillo, Estefania Aleman‐Navarro, G. Aleph Prieto, Yvonne Rosenstein, Jose J. Lozano‐Nuevo, Araceli Perez‐Lopez","doi":"10.1002/nep3.24","DOIUrl":"https://doi.org/10.1002/nep3.24","url":null,"abstract":"Abstract More than 670 million cases of coronavirus disease 2019 (COVID‐19) have been recorded worldwide in the 3 years since the start of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic. About 45% of survivors of COVID‐19 develop a syndrome known as long‐term COVID, in which symptoms persist even months after the acute infection. About 76% of patients with long COVID experience neurological manifestations. Moreover, patients who have survived COVID‐19 have an increased risk of cerebral venous thrombosis. This case report describes a 41‐year‐old woman who developed neurological manifestations associated with jugular vein thrombosis 24 h after administration of the Oxford–AstraZeneca (ChAdOx1 nCoV‐19) vaccine (AstraZeneca‐Serum Institute of India). She had been infected with SARS‐CoV‐2 three months before vaccination. Although initially suspected to be a case of vaccine‐induced immune thrombotic thrombocytopenia (VITT) in view of her recent vaccination, the patient did not have any hallmarks of VITT, such as thrombocytopenia, an increased d ‐dimer level, or antibodies against platelet factor‐4. Moreover, the neurological manifestations were associated with a high concentration of inflammatory cytokines, including interleukin (IL)‐6, IL‐17A, and IL‐21, and elevated neutrophil levels in cerebrospinal fluid, suggesting that inflammatory immune components had a role in the development of thrombotic events and pointing to an alternative diagnosis. In this case, the laboratory results indicated that the neurological manifestations associated with jugular vein thrombosis were not associated with VITT. Therefore, we propose that the thrombosis of the left jugular vein was a sequela of SARS‐CoV‐2 infection.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":" 39","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135243081","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":"Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)","authors":"Jie Liu, Heleen van Beusekom, Xian‐Le Bu, Gong Chen, Paulo Henrique Rosado de Castro, Xiaochun Chen, Xiaowei Chen, Andrew N. Clarkson, Tracy D. Farr, Yuhong Fu, Jianping Jia, Jukka Jolkkonen, Woojin Scott Kim, Paula Korhonen, Shen Li, Yajie Liang, Guang‐Hui Liu, Guiyou Liu, Yu‐Hui Liu, Tarja Malm, Xiaobo Mao, Joaquim Miguel Oliveira, Mike M. Modo, Pedro Ramos‐Cabrer, Karsten Ruscher, Weihong Song, Jun Wang, Xuanyue Wang, Yun Wang, Haitao Wu, Lize Xiong, Yi Yang, Keqiang Ye, Jin‐Tai Yu, Xin‐Fu Zhou, Marietta Zille, Colin L. Masters, Piotr Walczak, Boltze Johannes, Xunming Ji, Yan‐Jiang Wang","doi":"10.1002/nep3.23","DOIUrl":"https://doi.org/10.1002/nep3.23","url":null,"abstract":"Abstract The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease (AD) and associated socioeconomic burdens. Abnormal metabolism of amyloid‐β (Aβ) has been proposed as a significant pathomechanism in AD, supported by results of recent clinical trials using anti‐Aβ antibodies. Nonetheless, the cognitive benefits of the current treatments are limited. The etiology of AD is multifactorial, encompassing Aβ and tau accumulation, neuroinflammation, demyelination, vascular dysfunction, and comorbidities, which collectively lead to widespread neurodegeneration in the brain and cognitive impairment. Hence, solely removing Aβ from the brain may be insufficient to combat neurodegeneration and preserve cognition. To attain effective treatment for AD, it is necessary to (1) conduct extensive research on various mechanisms that cause neurodegeneration, including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level; (2) identify neuroprotective intervention targets against different neurodegeneration mechanisms; and (3) discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients. The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated, multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD. The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD, with the goal of halting or even reversing cognitive decline.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136237396","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}