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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of Basic medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for Clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

Critique and Comparison of Prevailing Consciousness Models with a Novel Embodied Cognition Model

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World Journal of Neuroscience 2018年第3期8卷 370-401页

作者： Ravinder Jerath Connor Beveridge charitable medical healthcare foundation Augusta GA USA

In order to produce insight to the current state of consciousness research, we provide a review of some of the more preeminent models of consciousness via a comparison of these theories with a novel holistic model. The main goal of this review is to present the advantages in theoretical power of an embodied cognition, metastable model of consciousness manifest in the Default Space Theory by comparing it to other popular brain-based metastable models that though provide important insight into the cognitive nature of consciousness, are incomplete in their model of an architecture of consciousness. The Default Space Theory is a world simulation model in which the thalamus fills in processed sensory information from corticothalamic feedback loops into an internal 3D matrix termed the default space. This article examines some of the most regarded brain-based, metastable consciousness models, the Operational Architectonics Theory of Brain-Mind, Global Workspace Theory, Information Integration Theory, and the Dynamic Core Hypothesis. Through an overview and critique of these models, we illustrate their insights and deficits, and discuss why the Default Space Theory is the most comprehensive theory of consciousness.

关键词： Default Space Metastability Consciousness Information Integration Global Workspace

Novel Bioelectric Mechanisms and Functional Significance of Peripheral and Central Entrainment by Respiration

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World Journal of Neuroscience 2018年第4期8卷 480-500页

作者： Ravinder Jerath Connor Beveridge charitable medical healthcare foundation Augusta GA USA

The human organism is a complex biological system with emergent properties that arise from the unified functional interactions among its diverse components. When studying the brain and body in light of modern biological systems approaches, one must analyze them in a holistic manner, putting aside reductionist models in order to understand how certain properties manifest from complex system interactions. The respiratory system is capable of continuously adapting to changes in the internal and external environment, making it one of the most integrated of physiological processes. We propose an additional respiratory process: respiration-derived electrical currents during inspiration that spread throughout the entire body maintaining homeostasis through entraining oscillatory activity, modulating cognitive processes, and modulating the autonomic nervous system. If these currents are indeed created in part from redox reactions occurring on a massive scale, then we assert they are a major aspect of an embodied cognitive framework. We propose that this potentially major source of organism integrity has been overlooked, and its application to medicine could drastically change how we understand human physiology, the autonomic nervous system, and the therapeutic treatment of various clinical disorders.

关键词： Bioelectric Respiration Embodied Cognition Oxidation Membrane Potential Neural Oscillation Hyperpolarization

Advances in genotypic antimicrobialresistance testing: a comprehensive review

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Science China Life Sciences 2025年第1期68卷 130-143页

作者： Boheng Duan Xianjun Zeng Junping Peng Huan Kui College of Nanchang University Department of Imaging The Second Affiliated Hospital of Nanchang University NHC Key Laboratory of Systems Biology of Pathogens National Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College Key Laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences & Peking Union Medical College Key Laboratory of Pathogen Infection Prevention and Control (Ministry of Education) State Key Laboratory of Respiratory Health and MultimorbidityNational Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College

Antimicrobial resistance(AMR) represents a substantial threat to global public health, complicating the treatment of common infections and leading to prolonged illness and escalated healthcare expenses. To effectively combat AMR, timely and accurate detection is crucial for AMR surveillance and individual-based therapy. Phenotypic antibiotic resistance testing(AST) has long been considered the gold standard in clinical applications, serving as the foundation for clinical AMR diagnosis and optimized therapy. It has significantly contributed to ensuring patients′ health and the development of novel antimicrobials. Despite advancements in automated culture-based AST technologies,inherent limitations impede the widespread use of phenotypic AST in AMR surveillance. Genotypic AST technologies offer a promising alternative option, exhibiting advantages of rapidity, high sensitivity, and specificity. With the continuous advancement and expanding applications of genotypic AST technologies, such as microfluidics, mass spectrometry, and high-resolution melting curve analysis, new vigor has been injected into the development and clinical implementation of genotypic AST technologies. In this narrative review, we discuss the principles, applications, and advancements of emerging genotypic AST methods in clinical settings. The comprehensive review aims to highlight the significant scientific potential of emerging genotypic AST technologies in clinical AMR diagnosis, providing insights to enhance existing methods and explore novel approaches.

关键词： antimicrobial resistance (AMR) genotypic antibiotic resistance testing (AST) AST technologies review

From Biological Rhythms to the Default Mode Network: What Lies beneath the Tip of the Iceberg of Mind?

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World Journal of Neuroscience 2019年第4期9卷 262-281页

作者： Ravinder Jerath Connor Beveridge charitable medical healthcare foundation Augusta GA USA

Our conscious day-to-day self is often described as the “tip of the iceberg” of a much greater cognitive system. The edge of the water divides the phenomenal self from the sub/unconscious underlying it. Similar to an iceberg, the unconscious activity below the water vastly outweighs the conscious activity above it. What exactly lies beneath the surface of this murky water is a tantalizing topic of research and theory. The current research predominantly focuses on the physiology of the brain and the default mode network has been identified as an intrinsic mode of functioning. It is well known that autonomic nervous system sympathovagal balance orchestrated by the central autonomic network is strongly associated with modulation of cardiac, respiratory rate and other visceral physiological activity. In this article, we use existing research and a novel theory to tie together the default mode network, the autonomic nervous system, and non-neural physiology to describe a hypothesis on a greater biological system from which intrinsic brain activity may be founded. This hypothesis is that intrinsic brain activity and connectivities are significantly founded on activity of the body. We review how cardiorespiratory and other rhythms and electrical activity of the body may modulate and even underlie fundamental activity of the human brain and ultimately the mind. A more holistic biological system that could interface the brain and body via mechanisms such as neurovascular coupling would more accurately describe the nature of neural systems. Greater knowledge on the association and interface of brain and body via isomorphic physiologic counterparts to mind may carry profound implications in understanding intrinsic activity of the brain, consciousness, mind, and mental illness.

关键词： Default Mode Network Embodied Cognition Mind Consciousness

Emerging Phenomenological and Biological Principles of Consciousness: Top Insights of Prevailing Models, Concepts, and Observations

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World Journal of Neuroscience 2019年第3期9卷 157-190页

作者： Ravinder Jerath Connor Beveridge charitable medical healthcare foundation Augusta GA USA

We are all aware that our experience is structured into left and right, up and down, and we can understand from our own experience that consciousness is unified into a singular whole. Although we can understand such basic phenomenological axioms of experience, there are many more principles that we cannot elucidate from our natural perspective alone. In this article, we review potential principles of consciousness revealed by prominent consciousness models, theories, and experimental observations such as the Default Space?Theory, Operational Architectonics Theory, and Integrated Information Theory,?which reveal biological and phenomenological foundations upon which consciousness is formed and maintained. The fundamental concepts we explore and consider worthy have largely emerged from commonalties shared by the various models which have gained attention. The concepts we review include the unity of consciousness, bioelectric operations as the substrate of consciousness, the emergence of a virtual 3D matrix, and the top-down dominance of perception.

关键词： Default Space Consciousness Thalamus Perception Operational Architectonics Integrated Information Theory Neural Synchrony World Simulation

Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

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Neural Regeneration Research 2025年第1期20卷 82-92页

作者： Stiven Roytman Rebecca Paalanen Giulia Carli Uros Marusic Prabesh Kanel Teus van Laar Nico I.Bohnen Department of Radiology University of MichiganAnn ArborMIUSA Department of Neurology University of MichiganAnn ArborMIUSA Morris K.Udall Center of Excellence for Parkinson’s Disease Research University of MichiganAnn ArborMIUSA Institute for Kinesiology Research Science and Research Centre KoperKoperSlovenia Department of Health Sciences Alma Mater Europaea–ECMMariborSlovenia Parkinson’s foundation Research Center of Excellence University of MichiganAnn ArborMIUSA Department of Neurology University of GroningenUniversity Medical Center GroningenGroningenThe Netherlands Neurology Service and GRECC VA Ann Arbor Healthcare SystemAnn ArborMIUSA

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging *** and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous *** effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory *** mechanisms which underpin the integration of these multisensory signals are the principal topic of the present *** multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older *** emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and *** the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s *** also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older ***,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

关键词： aging balance encephalography functional magnetic resonance imaging gait multisensory integration Parkinson’s disease positron emission tomography somatosensory vestibular visual

Conceptual Advances in the Default Space Model of Consciousness

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World Journal of Neuroscience 2018年第2期8卷 254-269页

作者： Ravinder Jerath Connor Beveridge Michael Jensen charitable medical healthcare foundation Augusta GA USA Augusta University Augusta GA USA

The default space model is a unified theory of consciousness that posits the brain and body together form the foundation of conscious experience that exists as a three dimensional internally generated simulation of reality termed the 3D dynamic default space. We have explored and developed the model in many publications and journals with a variety of academic specialties and its scope and concepts continue to broaden. In these publications, we have supported the concepts of the model through its ability to explain neuropsychological disorders, illusions, and everyday observations on consciousness. The model’s foundations in which the thalamus serves as a central hub networked with the brain and body by continuous, fast, membrane potential oscillations have been greatly expanded since its initial publication which we review within this article. Profound leaps forward in our theory include the nature of lateral inhibition in sensory perception, the nature of sensory organs acting as “smart screens”, and the correlation of respiration with mental atmosphere. Through reviewing the developing concepts expanding the theory since our major 2015 publication that laid the foundation of our theory, we hope to give readers a summarized update of where the theory currently stands in terms of its structure. We encourage readers to investigate these previous publications to gain further insight into our propositions. Through accurate models of consciousness, we may develop etiologies for countless neurological disorders, as well as improve treatments.

关键词： Lateral Inhibition Consciousness Default Space Respiration Vision