Neuroprotection最新文献

{"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}

{"title":"Join us on an amazing journey towards next-generation treatments for CNS disorders: Launch of Neuroprotection, a new high-quality journal in translational neuroscience.","authors":"Xuming Ji, Piotr Walczak, Heleen M M van Beusekom, Ana I Casas, Andrew Clarkson, Tracy Farr, Jukka Jolkkonen, Yajie Liang, Michel M Modo, Paulo H Rosado-de-Castro, Karsten Ruscher, Yan-Jiang Wang, Haitao Wu, Marietta Zille, Shen Li, Johannes Boltze","doi":"10.1002/nep3.8","DOIUrl":"10.1002/nep3.8","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"1 1","pages":"5-8"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10232621","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":"3D printing-based frugal manufacturing of glass pipettes for minimally invasive delivery of therapeutics to the brain.","authors":"Guanda Qiao, David Gulisashvili, Anna Jablonska, Guiling Zhao, Miroslaw Janowski, Piotr Walczak, Yajie Liang","doi":"10.1002/nep3.20","DOIUrl":"10.1002/nep3.20","url":null,"abstract":"<p><strong>Objective: </strong>Intracerebral delivery of agents in liquid form is usually achieved through commercially available and durable metal needles. However, their size and texture may contribute to mechanical brain damage. Glass pipettes with a thin tip may significantly reduce injection-associated brain damage but require access to prohibitively expensive programmable pipette pullers. This study is to remove the economic barrier to the application of minimally invasive delivery of therapeutics to the brain, such as chemical compounds, viral vectors, and cells.</p><p><strong>Methods: </strong>We took advantage of the rapid development of free educational online resources and emerging low-cost 3D printers by designing an affordable pipette puller (APP) to remove the cost obstacle.</p><p><strong>Results: </strong>We showed that our APP could produce glass pipettes with a sharp tip opening down to 20 μm or less, which is sufficiently thin for the delivery of therapeutics into the brain. A pipeline from pipette pulling to brain injection using low-cost and open-source equipment was established to facilitate the application of the APP.</p><p><strong>Conclusion: </strong>In the spirit of frugal science, our device may democratize glass pipette-puling and substantially promote the application of minimally invasive and precisely controlled delivery of therapeutics to the brain for finding more effective therapies of brain diseases.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"1 1","pages":"58-65"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170632","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":"Exploiting moderate hypoxia to benefit patients with brain disease: Molecular mechanisms and translational research in progress.","authors":"Hannelore Ehrenreich, Max Gassmann, Luise Poustka, Martin Burtscher, Peter Hammermann, Anna-Leena Sirén, Klaus-Armin Nave, Kamilla Miskowiak","doi":"10.1002/nep3.15","DOIUrl":"10.1002/nep3.15","url":null,"abstract":"<p><p>Hypoxia is increasingly recognized as an important physiological driving force. A specific transcriptional program, induced by a decrease in oxygen (O₂) availability, for example, inspiratory hypoxia at high altitude, allows cells to adapt to lower O₂ and limited energy metabolism. This transcriptional program is partly controlled by and partly independent of hypoxia-inducible factors. Remarkably, this same transcriptional program is stimulated in the brain by extensive motor-cognitive exercise, leading to a relative decrease in O₂ supply, compared to the acutely augmented O₂ requirement. We have coined the term \"functional hypoxia\" for this important demand-responsive, relative reduction in O₂ availability. Functional hypoxia seems to be critical for enduring adaptation to higher physiological challenge that includes substantial \"brain hardware upgrade,\" underlying advanced performance. Hypoxia-induced erythropoietin expression in the brain likely plays a decisive role in these processes, which can be imitated by recombinant human erythropoietin treatment. This article review presents hints of how inspiratory O₂ manipulations can potentially contribute to enhanced brain function. It thereby provides the ground for exploiting moderate inspiratory plus functional hypoxia to treat individuals with brain disease. Finally, it sketches a planned multistep pilot study in healthy volunteers and first patients, about to start, aiming at improved performance upon motor-cognitive training under inspiratory hypoxia.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"1 1","pages":"9-19"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10170540","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":"Ex vivo 100 μm isotropic diffusion MRI-based tractography of connectivity changes in the end-stage R6/2 mouse model of Huntington's disease.","authors":"Ashwinee Manivannan, Lesley M Foley, T Kevin Hitchens, Ivan Rattray, Gillian P Bates, Michel Modo","doi":"10.1002/nep3.14","DOIUrl":"10.1002/nep3.14","url":null,"abstract":"<p><strong>Background: </strong>Huntington's disease is a progressive neurodegenerative disorder. Brain atrophy, as measured by volumetric magnetic resonance imaging (MRI), is a downstream consequence of neurodegeneration, but microstructural changes within brain tissue are expected to precede this volumetric decline. The tissue microstructure can be assayed non-invasively using diffusion MRI, which also allows a tractographic analysis of brain connectivity.</p><p><strong>Methods: </strong>We here used ex vivo diffusion MRI (11.7 T) to measure microstructural changes in different brain regions of end-stage (14 weeks of age) wild type and R6/2 mice (male and female) modeling Huntington's disease. To probe the microstructure of different brain regions, reduce partial volume effects and measure connectivity between different regions, a 100 μm isotropic voxel resolution was acquired.</p><p><strong>Results: </strong>Although fractional anisotropy did not reveal any difference between wild-type controls and R6/2 mice, mean, axial, and radial diffusivity were increased in female R6/2 mice and decreased in male R6/2 mice. Whole brain streamlines were only reduced in male R6/2 mice, but streamline density was increased. Region-to-region tractography indicated reductions in connectivity between the cortex, hippocampus, and thalamus with the striatum, as well as within the basal ganglia (striatum-globus pallidus-subthalamic nucleus-substantia nigra-thalamus).</p><p><strong>Conclusions: </strong>Biological sex and left/right hemisphere affected tractographic results, potentially reflecting different stages of disease progression. This proof-of-principle study indicates that diffusion MRI and tractography potentially provide novel biomarkers that connect volumetric changes across different brain regions. In a translation setting, these measurements constitute a novel tool to assess the therapeutic impact of interventions such as neuroprotective agents in transgenic models, as well as patients with Huntington's disease.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"1 1","pages":"66-83"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41156258","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":"Monocytes in neonatal stroke and hypoxic‐ischemic encephalopathy: Pathophysiological mechanisms and therapeutic possibilities","authors":"P. M. Pimentel-Coelho","doi":"10.1002/nep3.22","DOIUrl":"https://doi.org/10.1002/nep3.22","url":null,"abstract":"Neonatal arterial ischemic stroke (NAIS) and neonatal hypoxic‐ischemic encephalopathy (HIE) are common causes of neurological impairments in infants, for which treatment options are very limited. NAIS and HIE induce an innate immune response that involves the recruitment of peripheral immune cells, including monocytes, into the brain. Monocytes and monocyte‐derived cells have the potential to contribute to both harmful and beneficial pathophysiological processes, such as neuroinflammation and brain repair, but their roles in NAIS and HIE remain poorly understood. Furthermore, recent evidence indicates that monocyte‐derived macrophages can persist in the brain for several months following NAIS and HIE in mice, with possible long‐lasting consequences that are still unknown. This review provides a comprehensive overview of the mechanisms of monocyte infiltration and their potential functions in the ischemic brain, focusing on HIE and NAIS. Therapeutic strategies targeting monocytes and the possibility of using monocytes for cell‐based therapies are also discussed.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82270533","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":"Liquid–liquid phase separation in synaptopathies","authors":"Huihui Jiang, Haitao Wu","doi":"10.1002/nep3.21","DOIUrl":"https://doi.org/10.1002/nep3.21","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88436025","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":"Aspects of xenobiotics and their receptors in stroke","authors":"Aishika Datta, Bijoyani Ghosh, Deepaneeta Sarmah, Antra Chaudhary, Anupom Borah, P. Bhattacharya","doi":"10.1002/nep3.9","DOIUrl":"https://doi.org/10.1002/nep3.9","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89674252","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}