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Mononuclear cell therapy of neonatal hypoxic-ischemic encephalopathy in preclinical versus clinical studies:A systematic analysis of therapeutic efficacy and study design

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Neuroprotection 2023年第2期1卷 143-159页

作者： Alexander M.Scrutton Francesca Ollis Johannes Boltze School of Life sciences University of WarwickCoventryUK Neurobiology Division MRC Laboratory of Molecular BiologyUniversity of CambridgeCambridgeUK

Background:Hypoxic-ischemic encephalopathy(HIE)is a devastating condition affecting around 8.5 in 1000 newborns *** hypothermia(TH)can reduce mortality and,to a limited extent,disability after ***,there is a need for new and effective treatment ***-based treatments using mononuclear cells(MNCs),which can be sourced from umbilical cord blood,are currently being *** promising preclinical results,there is currently no strong indicator for the clinical efficacy of the *** analysis aimed to provide potential explanations for this ***:A systematic review and meta-analysis were conducted according to the Preferred reporting Items for Systematic reviews and Meta-Analysis *** and clinical studies were retrieved from PubMed,Web of Science,Scopus,and *** using a predefined search strategy.A total of 17 preclinical and 7 clinical studies were *** analyzed overall MNC efficacy in preclinical trials,the methodological quality of preclinical trials,and relevant design features in preclinical versus clinical ***:There was evidence for MNC therapeutic efficacy in preclinical models of *** methodological quality of preclinical studies was not optimal,and statistical design quality was particularly ***,methodological quality was above the standard in other *** were significant differences in preclinical versus clinical study design including the use of TH as a baseline treatment(only in clinical studies)and much higher MNC doses being applied in preclinical ***:Based on the analyzed data,it is unlikely that therapeutic effect size is massively overestimated in preclinical *** is more plausible that the many design differences between preclinical and clinical trials are responsible for the so far lacking proof of the efficacy of MNC treatments in *** preclinical and clinical research is required

关键词： cell therapy hypoxic-ischemic encephalopathy mononuclear cells translational research treatment efficacy

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Activation of neurogenesis in the hippocampus is a novel therapeutic target for Alzheimer's disease

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Neuroprotection 2023年第2期1卷 139-142页

作者： Akihiko Taguchi Yuka Okinaka Akiko Takeda Takayuki Okamoto Johannes Boltze Carsten Claussen Sheraz Gul Department of regenerative Medicine research Foundation for Biomedical Research and Innovation at KobeHyogoJapan Department of Pharmacology Faculty of MedicineShimane UniversityIzumoShimaneJapan School of Life sciences University of WarwickCoventryUK Fraunhofer Institute for Translational Medicine and Pharmacology ITMP HamburgGermany Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD HamburgGermany

The pathologies associated with age-related brain dysfunction,including Alzheimer's disease(AD),Parkinson's disease,Lewy body dementia,and vascular dementia,often share similarities across multiple diseases.1 While various factors,such as amyloidβ,Tau protein,α-synuclein,chronic inflammation,and impaired cerebral microcirculation have been suggested as potential therapeutic targets,addressing a single factor is unlikely to be sufficient in preventing or treating age-related brain *** from these observations.

关键词： therapeutic Alzheimer impaired

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Preserving cognitive function in patients with Alzheimer's disease:The Alzheimer's disease neuroprotection research initiative(ADNrI)

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Neuroprotection 2023年第2期1卷 84-98页

作者： 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 Department of Neurology Daping HospitalThird Military Medical UniversityChongqingChina Chongqing Key Laboratory of Ageing and Brain Diseases ChongqingChina Division of Experimental Cardiology Department of CardiologyErasmus MCUniversity Medical CenterRotterdamThe Netherlands Institute of Brain and Intelligence Third Military Medical UniversityChongqingChina Guangdong-HongKong-Macao Institute of CNS regeneration(GHMICr) Jinan UniversityGuangzhouGuangdongChina Institute of Biomedical sciences Federal University of Rio de JaneiroRio de JaneiroRio de JaneiroBrazil Fujian Key Laboratory of Molecular Neurology Department of Neurology and GeriatricsFujian Institute of GeriatricsFujian Medical University Union HospitalInstitute of NeuroscienceFujian Medical UniversityFuzhouFujianChina Guangyang Bay Laboratory Chongqing Institute for Brain and IntelligenceChongqingChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina Department of Anatomy Brain Health Research Centre and Brain Research New ZealandUniversity of OtagoDunedinNew Zealand School of Life sciences University of NottinghamNottinghamUK Brain and Mind Centre&School of medical sciences The University of SydneySydneyNew South WalesAustralia Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalNational Clinical Research Center for Geriatric DiseasesCapital Medical UniversityBeijingChina A.I.Virtanen Institute for Molecular sciences University of Eastern FinlandKuopioFinland Department of Neurology and Psychiatry Beijing Shijitan HospitalCapital Medical UniversityBeijingChina Department of Diagnostic radiology and Nuclear Medicine University of Maryland School of MedicineBaltimoreMarylandUSA University of Chinese academy of sciences BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute of Brain Disorders Laboratory of Brain DisordersMinistry of Sci

The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease(AD)and associated socioeconomic *** metabolism of amyloid-β(Aβ)has been proposed as a significant pathomechanism in AD,supported by results of recent clinical trials using anti-Aβ***,the cognitive benefits of the current treatments are *** etiology of AD is multifactorial,encompassing Aβand tau accumulation,neuroinflammation,demyelination,vascular dysfunction,and comorbidities,which collectively lead to widespread neurodegeneration in the brain and cognitive ***,solely removing Aβfrom the brain may be insufficient to combat neurodegeneration and preserve *** 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 *** Alzheimer's Disease Neuroprotection research Initiative's objective is to facilitate coordinated,multidisciplinary efforts to develop systemic neuroprotective strategies to combat *** aim is to achieve mitigation of the full spectrum of pathological processes underlying AD,with the goal of halting or even reversing cognitive decline.

关键词： Alzheimer's disease early intervention neural regeneration neuroprotection systematic perspective

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Exploring novel experimental treatments for major neurodegenerative disorders

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Neuroprotection 2023年第2期1卷 81-83页

作者： Xunming Ji Piotr Walczak Johannes Boltze Beijing Institute of Brain Disorders Capital Medical UniversityBeijingChina Department of Diagnostic radiology and Nuclear Medicine Center for Advanced Imaging ResearchUniversity of MarylandBaltimoreMarylandUSA School of Life sciences University of WarwickCoventryUK

Acute and chronic neurodegenerative disorders such as ischemic stroke or Alzheimer's disease(AD)impose a major burden on patients,their relatives,caregivers,and health care systems in *** socioeconomic impact of neurodegenerative disorders is anticipated to escalate due to a globally ageing population and the increasing prevalence of sedentary lifestyle and inappropriate dietary *** the contrary.

关键词： Alzheimer's disease amyotrophic lateral sclerosis cell therapy cytoprotection extracellular vesicles neurodegeneration stroke

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Effects of immunological processes and mild ambient atmosphere alterations on the brain in health and disease

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Neuroprotection 2024年第3期2卷 179-181页

作者： Piotr Walczak Xunming Ji Shen Li Johannes Boltze Department of Diagnostic radiology and Nuclear Medicine Center for Advanced Imaging ResearchUniversity of MarylandBaltimoreMarylandUSA Beijing Institute of Brain Disorders Capital Medical UniversityBeijingChina School of Life sciences University of WarwickCoventryUK

Immunological processes in the brain and periphery are well known to affect brain function in health and ***,our knowledge about the crosstalk between the immune system and the central nervous system is far from being *** research in this field is uncovering the complex interactions between these"supersystems,"often involving additional organs such as the gut with its microbiome,as well as pathophysiological factors such as hyperglycemia,hypertension,or dyslipidemia.

关键词： alterations organs ambient

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