Translational Research in Traumatic Brain Injury

Translational Research in Traumatic Brain Injury
Author: Daniel Laskowitz
Publisher: CRC Press
Total Pages: 388
Release: 2016-04-21
Genre: Medical
ISBN: 1498766579

Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme

The Neuropathology of Huntington’s Disease: Classical Findings, Recent Developments and Correlation to Functional Neuroanatomy

The Neuropathology of Huntington’s Disease: Classical Findings, Recent Developments and Correlation to Functional Neuroanatomy
Author: Udo Rüb
Publisher: Springer
Total Pages: 154
Release: 2015-09-29
Genre: Medical
ISBN: 331919285X

This monograph describes the progress in neuropathological HD research made during the last century, the neuropathological hallmarks of HD and their pathogenic relevance. Starting with the initial descriptions of the progressive degeneration of the striatum as one of the key events in HD, the worldwide practiced Vonsattel HD grading system of striatal neurodegeneration will be outlined. Correlating neuropathological data with results on the functional neuroanatomy of the human brain, subsequent chapters will highlight recent HD findings: the neuronal loss in the cerebral neo-and allocortex, the neurodegeneration of select thalamic nuclei, the affection of the cerebellar cortex and nuclei, the involvement of select brainstem nuclei, as well as the pathophysiological relevance of these pathologies for the clinical picture of HD. Finally, the potential pathophysiological role of neuronal huntingtin aggregations and the most important and enduring challenges of neuropathological HD research are discussed.

The CA3 Region of the Hippocampus: How is it? What is it for? How does it do it?

The CA3 Region of the Hippocampus: How is it? What is it for? How does it do it?
Author: Enrico Cherubini
Publisher: Frontiers Media SA
Total Pages: 167
Release: 2015-08-19
Genre: Hippocampus (Brain)
ISBN: 2889196313

The CA3 hippocampal region receives information from the entorhinal cortex either directly from the perforant path or indirectly from the dentate gyrus via the mossy fibers (MFs). According to their specific targets (principal/mossy cells or interneurons), MFs terminate with large boutons or small filopodial extensions, respectively. MF-CA3 synapses are characterized by a low probability of release and pronounced frequency-dependent facilitation. In addition MF terminals are endowed with mGluRs that regulate their own release. We will describe the intrinsic membrane properties of pyramidal cells, which can sometimes fire in bursts, together with the geometry of their dendritic arborization. The single layer of pyramidal cells is quite distinct from the six-layered neocortical arrangement. The resulting aligned dendrites provides the substrate for laminated excitatory inputs. They also underlie a precise, diversity of inhibitory control which we will also describe in detail. The CA3 region has an especially rich internal connectivity, with recurrent excitatory and inhibitory loops. In recent years both in vivo and in vitro studies have allowed to better understand functional properties of the CA3 auto-associative network and its role in information processing. This circuit is implicated in encoding spatial representations and episodic memories. It generates physiological population synchronies, including gamma, theta and sharp-waves that are presumed to associate firing in selected assemblies of cells in different behavioral conditions. The CA3 region is susceptible to neurodegeneration during aging and after stresses such as infection or injury. Loss of some CA3 neurones has striking effects on mossy fiber inputs and can facilitate the generation of pathologic synchrony within the CA3 micro-circuit. The aim of this special topic is to bring together experts on the cellular and molecular mechanisms regulating the wiring properties of the CA3 hippocampal microcircuit in both physiological and pathological conditions, synaptic plasticity, behavior and cognition.We will particularly emphasize the dual glutamatergic and GABAergic phenotype of MF-CA3 synapses at early developmental stages and the steps that regulate the integration of newly generated neurons into the adult dentate gyrus-CA3 circuit.

Human Neural Stem Cells

Human Neural Stem Cells
Author: Leonora Buzanska
Publisher: Springer
Total Pages: 334
Release: 2018-09-12
Genre: Science
ISBN: 3319934856

This book summarizes early pioneering achievements in the field of human neural stem cell (hNSC) research and combines them with the latest advances in stem cell technology, including reprogramming and gene editing. The powerful potential of hNSC to generate and repair the developing and adult CNS has been confirmed by numerous experimental in vitro and in vivo studies. The book presents methods for hNSC derivation and discusses the mechanisms underlying NSC in vitro fate decisions and their in vivo therapeutic mode of action. The long-standing dogma that the human central nervous system (CNS) lacks the ability to regenerate was refuted at the end of the 20th century, when evidence of the presence of neurogenic zones in the adult human brain was found. These neurogenic zones are home to human neural stem cells (hNSCs), which are capable of self-renewing and differentiating into neurons, astrocytes and oligodendrocytes. NSCs isolated from human CNS have a number of clinical advantages, especially the innate potential to differentiate into functional neural cells. Nevertheless, their full clinical exploitation has been hindered by limited access to the tissue and low expansion potential. The search for an alternative to CNS sources of autologous, therapeutically competent hNSCs was the driving force for the many studies proving the in vitro plasticity of different somatic stem cells to generate NSCs and their functional progeny. Now the era of induced pluripotent stem cells has opened entirely new opportunities to achieve research and therapeutic goals with the aid of hNSCs.

Cyclin Dependent Kinase 5 (Cdk5)

Cyclin Dependent Kinase 5 (Cdk5)
Author: Nancy Y. Ip
Publisher: Springer Science & Business Media
Total Pages: 326
Release: 2009-02-28
Genre: Medical
ISBN: 0387788875

Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.

Astrocytes in (Patho)Physiology of the Nervous System

Astrocytes in (Patho)Physiology of the Nervous System
Author: Vladimir Parpura
Publisher: Springer Science & Business Media
Total Pages: 701
Release: 2008-12-11
Genre: Medical
ISBN: 0387794921

Astrocytes were the original neuroglia that Ramón y Cajal visualized in 1913 using a gold sublimate stain. This stain targeted intermediate filaments that we now know consist mainly of glial fibrillary acidic protein, a protein used today as an astrocytic marker. Cajal described the morphological diversity of these cells with some ast- cytes surrounding neurons, while the others are intimately associated with vasculature. We start the book by discussing the heterogeneity of astrocytes using contemporary tools and by calling into question the assumption by classical neuroscience that neurons and glia are derived from distinct pools of progenitor cells. Astrocytes have long been neglected as active participants in intercellular communication and information processing in the central nervous system, in part due to their lack of electrical excitability. The follow up chapters review the “nuts and bolts” of ast- cytic physiology; astrocytes possess a diverse assortment of ion channels, neu- transmitter receptors, and transport mechanisms that enable the astrocytes to respond to many of the same signals that act on neurons. Since astrocytes can detect chemical transmitters that are released from neurons and can release their own extracellular signals there is an increasing awareness that they play physiological roles in regulating neuronal activity and synaptic transmission. In addition to these physiological roles, it is becoming increasingly recognized that astrocytes play critical roles during pathophysiological states of the nervous system; these states include gliomas, Alexander disease, and epilepsy to mention a few.

Glial Physiology and Pathophysiology

Glial Physiology and Pathophysiology
Author: Alexei Verkhratsky
Publisher: John Wiley & Sons
Total Pages: 473
Release: 2013-01-31
Genre: Medical
ISBN: 1118402057

Glial Physiology and Pathophysiology provides a comprehensive, advanced text on the biology and pathology of glial cells. Coverae includes: the morphology and interrelationships between glial cells and neurones in different parts of the nervous systems the cellular physiology of the different kinds of glial cells the mechanisms of intra- and inter-cellular signalling in glial networks the mechanisms of glial-neuronal communications the role of glial cells in synaptic plasticity, neuronal survival and development of nervous system the cellular and molecular mechanisms of metabolic neuronal-glial interactions the role of glia in nervous system pathology, including pathology of glial cells and associated diseases - for example, multiple sclerosis, Alzheimer's, Alexander disease and Parkinson's Neuroglia oversee the birth and development of neurones, the establishment of interneuronal connections (the 'connectome'), the maintenance and removal of these inter-neuronal connections, writing of the nervous system components, adult neurogenesis, the energetics of nervous tissue, metabolism of neurotransmitters, regulation of ion composition of the interstitial space and many, many more homeostatic functions. This book primes the reader towards the notion that nervous tissue is not divided into more important and less important cells. The nervous tissue functions because of the coherent and concerted action of many different cell types, each contributing to an ultimate output. This reaches its zenith in humans, with the creation of thoughts, underlying acquisition of knowledge, its analysis and synthesis, and contemplating the Universe and our place in it. An up-to-date and fully referenced text on the most numerous cells in the human brain Detailed coverage of the morphology and interrelationships between glial cells and neurones in different parts of the nervous system Describes the role og glial cells in neuropathology Focus boxes highlight key points and summarise important facts Companion website with downloadable figures and slides

Polyglutamine Disorders

Polyglutamine Disorders
Author: Clévio Nóbrega
Publisher: Springer
Total Pages: 467
Release: 2018-02-09
Genre: Medical
ISBN: 3319717790

This book provides a cutting-edge review of polyglutamine disorders. It primarily focuses on two main aspects: (1) the mechanisms underlying the pathologies’ development and progression, and (2) the therapeutic strategies that are currently being explored to stop or delay disease progression. Polyglutamine (polyQ) disorders are a group of inherited neurodegenerative diseases with a fatal outcome that are caused by an abnormal expansion of a coding trinucleotide repeat (CAG), which is then translated in an abnormal protein with an elongated glutamine tract (Q). To date, nine polyQ disorders have been identified and described: dentatorubral-pallidoluysian atrophy (DRPLA); Huntington’s disease (HD); spinal–bulbar muscular atrophy (SBMA); and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). The genetic basis of polyQ disorders is well established and described, and despite important advances that have opened up the possibility of generating genetic models of the disease, the mechanisms that cause neuronal degeneration are still largely unknown and there is currently no treatment available for these disorders. Further, it is believed that the different polyQ may share some mechanisms and pathways contributing to neurodegeneration and disease progression.

Mesenchymal Stem Cell Derived Exosomes

Mesenchymal Stem Cell Derived Exosomes
Author: Yaoliang Tang
Publisher: Academic Press
Total Pages: 287
Release: 2015-09-02
Genre: Science
ISBN: 0128004975

Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. Introduces the MSC-exosome mediated cell-cell communication Covers the major functional benefits in current MSC-derived exosome studies Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies