Neuroprotection最新文献

{"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":4.1,"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":"5-22"},"PeriodicalIF":4.1,"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":"Pedro M Pimentel-Coelho","doi":"10.1002/nep3.22","DOIUrl":"10.1002/nep3.22","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"31 1","pages":"66-79"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82270533","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":"Liquid-liquid phase separation in synaptopathies.","authors":"Huihui Jiang, Haitao Wu","doi":"10.1002/nep3.21","DOIUrl":"10.1002/nep3.21","url":null,"abstract":"<p><p>Liquid-liquid phase separation has emerged as an important mechanism for regulating cell activity by promoting the formation of membrane-less condensates. In the nervous system, the formation of distinct molecular condensates via phase separation is involved in synaptic assembly and function. Disruption of phase separation is associated with several disease states, such as cancer, neurodegenerative disorders, and neurodevelopmental disorders. This review summarizes the function of phase separation in the assembly and plasticity of the synapse, discusses the role of abnormal phase separation in neurological diseases, and proposes potential treatment options for these neurological diseases based on phase separation.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"130 1","pages":"43-54"},"PeriodicalIF":4.1,"publicationDate":"2023-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88436025","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":"Aspects of xenobiotics and their receptors in stroke.","authors":"Aishika Datta, Bijoyani Ghosh, Deepaneeta Sarmah, Antra Chaudhary, Anupom Borah, Pallab Bhattacharya","doi":"10.1002/nep3.9","DOIUrl":"10.1002/nep3.9","url":null,"abstract":"<p><p>Stroke is devastating and the second leading cause of disability and death worldwide. The pathophysiology of stroke is intricate involving oxidative stress, ionic imbalance, and excitotoxicity leading to cell death. The current therapeutic strategies for ischemic stroke primarily aim to restore cerebral blood flow by removing clots using intravenous thrombolysis and mechanical thrombectomy. However, hemorrhagic stroke requires different therapeutic interventions, where intravenous thrombolysis worsens the persistent condition. Nevertheless, the present treatment strategies do not provide effective neuroprotection as they have limitations such as narrow time window, specialized clinics and personnel, and higher expense. Therefore, studies on novel therapeutic strategies that can render neuroprotection over an extended time with minimum adverse effects are solicited. Xenobiotics are agents that are foreign to the biological system but can regulate their metabolism by binding to different xenobiotic receptors (XRs) to produce toxic substances. Modulation of XRs in different preclinical studies have shown benefits in the stroke outcome. Therefore, targeting XRs may be a future therapeutic strategy for stroke intervention. The present review briefly discusses various implications of xenobiotics and their receptors to evolve as a potential therapeutic target for prospective use as an adjunctive therapy for stroke.</p>","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"1 1","pages":"23-34"},"PeriodicalIF":4.1,"publicationDate":"2022-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89674252","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":"Join us on an amazing journey towards next-generation treatments for CNS disorders: Launch of <i>Neuroprotection</i>, a new high-quality journal in translational neuroscience.","authors":"Xunming 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":"1-4"},"PeriodicalIF":4.1,"publicationDate":"2022-09-03","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":"Current Therapeutic Approaches from Imidazoline and Opioid Receptors Modulators in Neuroprotection","authors":"L. Mititelu-Tarțău, M. Bogdan, V. Gheorman, L. Foia, Ancuța Goriuc, G. Rusu, B. R. Buca, L. Pavel, A. Cristofor, C. Tartau, G. Popa","doi":"10.5772/INTECHOPEN.81951","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.81951","url":null,"abstract":"Due to brain plasticity, the nervous system is capable of manifesting behavioral variations, adapted to the influences from both external and internal environment. Multiple neurotransmitters are involved in the mediation of pathological processes at the molecular, cellular, regional, and interregional levels participating in cerebral plasticity, their intervention being responsible for various structural, functional, and behavioral disturbances. The current therapeutic strategies in neuroprotection aim at blocking on different levels, the molecular cascades of the pathophysiological mechanisms responsible for neuronal dysfunctions and ultimately for neuronal death. Different agents influencing these neurotransmitters have demonstrated beneficial effects in neurogenesis and neuroprotection, proved in experimental animal models of focal and global ischemic injuries. Serotonin, dopamine, glutamate, N-methyl-D-aspartate, and nitric oxide have been shown to play a significant role in modulating nervous system injuries. The imidazoline system is one of the important systems involved in human brain functioning. Experimental investigations have revealed the cytoprotective effects of imidazoline I2 receptor ligands against neuronal injury induced by hypoxia in experimental animals. The neuroprotective effects were also highlighted for kappa and delta receptors, whose agonists demonstrated the ability to reduce architectural lesions and to recover neuronal functions of animals with experimentally induced brain ischemia.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87002104","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":"Introductory Chapter: Concept of Neuroprotection - A New Perspective","authors":"R. Chang, Y. Ho","doi":"10.5772/INTECHOPEN.85631","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.85631","url":null,"abstract":"","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88211288","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 Role and Development of the Antagonist of Adenosine A2A in Parkinson’s Disease","authors":"W. Aryati, Nabilah Nurtika Salamah, Rezi Riadhi Syahdi, Arry Yanuar","doi":"10.5772/INTECHOPEN.84272","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.84272","url":null,"abstract":"Adenosine is a neuromodulator that regulates the body’s response to dopamine and another neurotransmitter in the brain that is responsible for motoric, emotion, learning, and memory function. Adenosine is a G-protein-coupled receptor and has four subtypes, which are A 1, A 2A , A 2B , and A 3 . Adenosine A 2A is located in the striatum of the brain. Antagonist interferes with GABA releasing, modulates acetyl-choline and releases dopamine, and also facilitates dopamine receptor’s signaling. Therefore, it can reduce motoric symptoms in Parkinson’s disease. Adenosine A 2A antagonist is also believed to have neuroprotective effects. Several compounds have been reported and have undergone clinical test as selective adenosine A 2A antagonists, including istradefylline, preladenant, tozadenant, vipadenant, ST-1535, and SYN-115. Nonselective adenosine A 2A antagonists from natural compounds are caffeine and theophylline. ,","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72890883","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":"Protecting the Aging Retina","authors":"S. Nian, A. Lo","doi":"10.5772/INTECHOPEN.82330","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.82330","url":null,"abstract":"Aging retina, notably the aging macula, is prone to develop degenerative diseases, such as age-related macular degeneration (AMD), the leading cause of visual loss in individuals aged 65 or above in developed countries. However, current treatments are very limited. Since degeneration, dysfunction, and death of retinal neurons are demonstrated in the pathogenesis of AMD, neuroprotective strategies could serve as a possible way to treat AMD. In this chapter, we will briefly introduce risk factors, pathophysiology, affected neurons, classification, clinical manifestation, and current treatments of AMD. Finally, neuroprotection in both AMD animal models and patients will be discussed.","PeriodicalId":74291,"journal":{"name":"Neuroprotection","volume":"253 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78381217","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}