Overactive Bladder Symptoms Within Nervous System: A Focus on Etiology

Overactive bladder (OAB) is a common debilitating condition characterized by urgency symptoms with detrimental effects on the quality of life and survival. The exact etiology of OAB is still enigmatic, and none of therapeutic approaches seems curative. OAB is generally regarded as a separate syndrome, whereas in clinic, OAB symptoms could be found in numerous diseases of other non-urogenital systems, particularly nervous system. The OAB symptoms in neurological diseases are often poorly recognized and inadequately treated. This review provided a comprehensive overview of recent findings related to the neurogenic OAB symptoms. Relevant neurological diseases could be mainly divided into seven kinds as follows: multiple sclerosis and related neuroinflammatory disorders, Parkinson’s diseases, multiple system atrophy, spinal cord injury, dementia, peripheral neuropathy, and others. Concurrently, we also summarized the hypothetical reasonings and available animal models to elucidate the underlying mechanism of neurogenic OAB symptoms. This review highlighted the close association between OAB symptoms and neurological diseases and expanded the current knowledge of pathophysiological basis of OAB. This may increase the awareness of urological complaints in neurological disorders and inspire robust therapies with better outcomes.

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Anatomy of the Opioid-Systems of the Brain

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100045261 ◽

1984 ◽

Vol 11 (1) ◽

pp. 14-23 ◽

Cited By ~ 17

Author(s):

Karl M. Knigge ◽

Shirley A. Joseph

Keyword(s):

Nervous System ◽

Brain Research ◽

Current Knowledge ◽

Neurological Diseases ◽

Pituitary Hormones ◽

Isolation And Identification ◽

Cord Injury ◽

The Central Nervous System ◽

Releasing Factors ◽

The Brain

In 1969, Roger Guillemin and Andrew Schally independently reported the isolation and identification of the first hypothalamic neuropeptide, thyrotropin releasing factor (TRF). Following this landmark event in neuroendocrinology the ensuing years have witnessed a cascade of isolations of new neuropeptides and a virtual revolution in neurobiology. The discipline of neuroendocrinology has been remarkably impacted by the evidence that all of the “hypophysiotrophic” releasing factors presently identified are distributed widely throughout the brain with neurotransmitter or neuromodulator roles quite different from their actions of regulating the secretion of pituitary hormones. The study of these neuropeptide systems in activity of the central nervous system looms as one of the most exciting and significant eras in brain research. Although it is premature to assign specific roles for the presently known neuropeptides in pathogenesis of neurological diseases, our limited current knowledge already points to a numberof syndromes and clinical disorders which may be related to neuropeptide imbalance. Congential insensitivity to pain undoubtedly involves several peptide systems including Substance P, enkephalin, somatostatin and the endorphins. The opiocortins (β-endorphin, ACTH) of the brain as well as those of the pituitary gland are directly involved in the homeostatic mechanisms brought into action by such trauma as brain and spinal cord injury, septic shock and hemorrhage. The role of peptides in regulation of cerebral circulation will likely be identified with the etiology of stroke and the production of painful hemicranial syndromes. Among the most prevelant disorders of the human nervous system are the dementias and psychoses (Alzheimer’s disease, schizophrenia); subtle changes in brain peptide and receptor activity are being considered as responsible contributors to these diseases.

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Endogenous stem cell proliferation after central nervous system injury: alternative therapeutic options

Neurosurgical FOCUS ◽

10.3171/foc.2005.19.3.2 ◽

2005 ◽

Vol 19 (3) ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Nicholas C. Bambakidis ◽

Nicholas Theodore ◽

Peter Nakaji ◽

Adrian Harvey ◽

Volker K. H. Sonntag ◽

...

Keyword(s):

Central Nervous System ◽

Cell Proliferation ◽

Nervous System ◽

Stem Cell ◽

Neurological Diseases ◽

Cell Populations ◽

Stem Cell Proliferation ◽

Cord Injury ◽

Stem Cell Populations ◽

Endogenous Stem Cell

The continuous regeneration of glial cells arising from endogenous stem cell populations in the central nervous system (CNS) occurs throughout life in mammals. In the ongoing research to apply stem cell therapy to neurological diseases, the capacity to harness the multipotential ability of endogenous stem cell populations has become apparent. Such cell populations proliferate in response to a variety of injury states in the CNS, but in the absence of a supportive microenvironment they contribute little to any significant behavioral recovery. In the authors' laboratory and elsewhere, recent research on the regenerative potential of these stem cells in disease states such as spinal cord injury has demonstrated that the cells' proliferative potential may be greatly upregulated in response to appropriate growth signals and exogenously applied trophic factors. Further understanding of the potential of such multipotent cells and the mechanisms responsible for creating a favorable microenvironment for them may lead to additional therapeutic alternatives in the setting of neurological diseases. These therapies would require no exogenous stem cell sources and thus would avoid the ethical and moral considerations regarding their use. In this review the authors provide a brief overview of the enhancement of endogenous stem cell proliferation following neurological insult.

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Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

Mediators of Inflammation ◽

10.1155/2017/9478542 ◽

2017 ◽

Vol 2017 ◽

pp. 1-14 ◽

Cited By ~ 47

Author(s):

Ilse Bollaerts ◽

Jessie Van houcke ◽

Lien Andries ◽

Lies De Groef ◽

Lieve Moons

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Axonal Regeneration ◽

Current Knowledge ◽

Cord Injury ◽

The Central Nervous System ◽

Novel Therapeutic Strategies ◽

The Impact ◽

Vertebrate Central Nervous System

Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies.

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Revisit the Cellular Transmission and Emerging Techniques in Understanding the Mechanisms of Proteinopathies

Frontiers in Neuroscience ◽

10.3389/fnins.2021.781722 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jinwen Jiang ◽

Yu Liu ◽

Qihui Wu

Keyword(s):

Gene Expression ◽

Nervous System ◽

Single Cell ◽

Expression Profiles ◽

Expression Patterns ◽

Molecular Taxonomy ◽

Gene Expression Profiles ◽

Underlying Mechanism ◽

Signal Pathways ◽

Parkinson’S Diseases

Alzheimer’s and Parkinson’s diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in mediating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.

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Betulinic Acid Inhibits ROS-Mediated Pyroptosis in Spinal Cord Injury by Augmenting Autophagy via the AMPK-mTOR-TFEB Signaling Pathway

10.21203/rs.3.rs-100352/v1 ◽

2020 ◽

Author(s):

Chenyu Wu ◽

Huanwen Chen ◽

Rong Zhuang ◽

Yongli Wang ◽

Xinli Hu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Signaling Pathway ◽

Betulinic Acid ◽

Neurological Diseases ◽

Underlying Mechanism ◽

Autophagy Flux ◽

Wide Range ◽

Cord Injury

Abstract Background：Spinal cord injury (SCI) results in a wide range of disabilities. Its complex pathophysiological process limits the effectiveness of many clinical treatments. Betulinic acid (BA) has been shown to be an effective treatment for some neurological diseases, but it has not been studied in SCI. In this study, we assessed the role of BA in SCI and investigated its underlying mechanism. Methods：Using a mouse model of SCI, survival and functional outcomes following injury were assessed. Western blotting, ELISA, and immunofluorescence techniques were employed to analyze levels of autophagy, mitophagy, and pyroptosis; ROS- and AMPK-related signaling pathways were also examined. Results：Our results showed that BA significantly improves functional recovery following SCI. Furthermore, autophagy, mitophagy, ROS-activity and pyroptosis were implicated in the mechanism of BA in the treatment of SCI. Specifically, our results suggest that BA restored autophagy flux following injury, which induces mitophagy to eliminate the accumulation of ROS and subsequently inhibits pyroptosis. Further mechanistic studies revealed that BA likely regulates autophagy and mitophagy via the AMPK-mTOR-TFEB signaling pathway. Conclusion: BA can significantly promote the recovery following SCI and that it may be a promising therapy for SCI.

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The Early Development of Neuroscience in Canada

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100047065 ◽

1985 ◽

Vol 12 (3) ◽

pp. 221-229 ◽

Cited By ~ 5

Author(s):

Herbert H. Jasper

Keyword(s):

Nervous System ◽

World War Ii ◽

Early Development ◽

Neurological Diseases ◽

Close Association ◽

Rapid Development ◽

50Th Anniversary ◽

The United States ◽

International Institute ◽

Montreal Neurological Institute

A review of some of my personal recollections and research into the early development of neuroscience in Canada seems particularly appropriate at this time since we have just celebrated the 50th anniversary of the founding of the Montreal Neurological Institute which not only played a leading role in the early development of neuroscience in Canada, but also had considerable impact upon the development of both clinical and basic neuroscience throughout the world. The concept of the fusion of all the varied disciplines concerned with studies of the nervous system into one integrated “neuroscience” as we know it today in the Society for Neuroscience was not known when Dr. Penfield established the Montreal Neurological Institute with this in mind. He recruited colleagues in neurochemistry, neurophysiology, neuroanatomy, pathology, and neuropsychology to work in close association with clinical neurologists and neurosurgeons. Fellows were attracted from many countries for training in all of these disciplines and shared his dream of an integrated neuroscience aimed at a better understanding of the function of the nervous system underlying behaviour and mental function and more rational treatment of neurological diseases.The inspiration, enthusiasm, and tireless determination of Dr. Penfield during the difficult times for the initial few years and during the most productive years of rapid growth following World War II, helped develop the Institute into a leading centre for research and training of neuroscientists in Canada, and also served as a catalyst for the rapid development of neuroscience in other centres throughout Canada and the United States. As one of my French colleagues has expressed it, the Institute was the “mother house” of neuroscience in Canada. It soon became a truly international institute of worldwide reknown.

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STochastic Optical Reconstruction Microscopy (STORM) reveals the nanoscale organization of pathological aggregates in human brain

10.21203/rs.3.rs-22385/v1 ◽

2020 ◽

Author(s):

Philippe Codron ◽

Franck Letournel ◽

Serge Marty ◽

Alexia Bodin ◽

Laurence Renaud ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Human Brain ◽

Neurodegenerative Disorders ◽

Neurological Diseases ◽

Super Resolution ◽

Tissue Samples ◽

Stochastic Optical Reconstruction Microscopy ◽

Parkinson’S Diseases ◽

Optical Reconstruction

Abstract Background Histological analysis of brain tissue samples provide valuable information about the pathological processes leading to common neurodegenerative disorders such as Alzheimer’s or Parkinson’s diseases. In particular, high resolution and specific analysis of intra-neuronal lesions is crucial to understand the pathogenesis and progression of these diseases. In this context, the development of novel imaging approaches is a current challenge in neuroscience. Methods To this end, we used a recent super-resolutive imaging technique called STochastic Optical Reconstruction Microscopy (STORM) to analyze human brain sections. We combined STORM cell imaging protocols with neuropathological techniques and imaged cryopreserved brain samples from control subjects and patients with neurodegenerative diseases. Results This approach allowed us to perform 2D-, 3D- and two-color-STORM in central nervous system tissue sections, and to characterize with a nanometer-scale precision the architecture of physiological and pathological structures in neocortex, white matter and brainstem samples. STORM proved to be particularly effective to visualize the organization of dense protein inclusions, and allowed us to image with unprecedented details Aβ, Tau, α-synuclein and TDP-43 pathological aggregates within the central nervous system of patients with neurodegenerative disorders. Conclusions STORM imaging of human brain samples opens further gates to a more comprehensive understanding of the underlying mechanisms responsible for common neurological diseases. The convenience of this technique should open a straightforward extension of its application for super-resolution imaging of the human brain, with promising avenues to current challenges in neuroscience.

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Generating microglia from human pluripotent stem cells: novel in vitro models for the study of neurodegeneration

Molecular Neurodegeneration ◽

10.1186/s13024-019-0347-z ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 6

Author(s):

Anna M. Speicher ◽

Heinz Wiendl ◽

Sven G. Meuth ◽

Matthias Pawlowski

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Drug Testing ◽

Disease Modeling ◽

Current Knowledge ◽

Neurological Diseases ◽

Human Pluripotent Stem Cells ◽

Comprehensive Overview ◽

Human Microglia

AbstractMicroglia play an essential role for central nervous system (CNS) development and homeostasis and have been implicated in the onset, progression, and clearance of numerous diseases affecting the CNS. Previous in vitro research on human microglia was restricted to post-mortem brain tissue-derived microglia, with limited availability and lack of scalability. Recently, the first protocols for the generation of microglia from human pluripotent stem cells have become available, thus enabling the implementation of powerful platforms for disease modeling, drug testing, and studies on cell transplantation. Here we give a detailed and comprehensive overview of the protocols available for generating microglia from human pluripotent stem cells, highlighting the advantages, drawbacks, and operability and placing them into the context of current knowledge of human embryonic development. We review novel insights into microglia biology and the role of microglia in neurological diseases as drawn from the new methods and provide an outlook for future lines of research involving human pluripotent stem cell-derived microglia.

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Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications

Stem Cells International ◽

10.1155/2016/4869071 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Maria Giuseppina Cefalo ◽

Andrea Carai ◽

Evelina Miele ◽

Agnese Po ◽

Elisabetta Ferretti ◽

...

Keyword(s):

Nervous System ◽

Brain Tumors ◽

Large Scale ◽

Neurological Diseases ◽

Clinical Use ◽

Therapeutic Approaches ◽

Cell Based Therapy ◽

Human Ipscs ◽

Cord Injury ◽

Human Ipsc

Many central nervous system (CNS) diseases including stroke, spinal cord injury (SCI), and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting.

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