Open Access Medical Books



Edited by Tao Sun .

452 pages .
Open Access .

We have made exciting progress in understanding the neural stem cells (NSCs) in the past twenty years. We have learned what genes control NSC proliferation and differentiation, discovered how to culture NSCs and trace their lineage in a culture dish, and have even developed methods to either stimulate endogenous NSCs to repair damaged neurons or transplant cultured NSCs to damaged regions in the central nervous system (CNS). Research from neurodevelopmental biologists using various invertebrate and vertebrate models, in particular rodents, has advanced the NSC field and accelerated therapy using NSCs.
The notion of germinal cells in the neurogenic region, such as the ventricular zone (VZ) in embryonic human brains, came very early, in the 1870s. Later on, the advance of labeling techniques, in particular using the DNA replication marker [3H]-thymidine, allowed scientists to visualize dividing progenitors in primate and rodent brains. In embryonic mammalian brains, neuroepithelial cells are the first identified proliferating cells and they are in fact NSCs. These NSCs are then transformed into radial glial cells, which are now known as neural progenitors, and then intermediate progenitors. The proper proliferation of these progenitors is believed to be important for controlling brain size. Similar NSCs are also identified in other regions in the CNS, such as the spinal cord.
The adult brain has long been recognized as a hard-wired system that neither generates new neurons, nor consists of NSCs. However, the observation of new neurons in the song bird brain has changed our view of adult neurogenesis. Using [3H]-thymidine labeling, dividing cells were detected on the wall of the lateral ventricle and, 30 days later, new neurons were detected in the high vocal center (HVC), a region that is believed to be responsible for song production. Furthermore, dividing cells were observed in the SVZ region of adult rodent brains and in the dentate gyrus (DG) region in the hippocampus of rodent and even human brains.
Thus, in contrast to the previously held view of the hard-wired adult brain, new  neurons are constantly generated in the SVZ and then migrate along the rostral migratory stream (RMS) into the olfactory bulb and the DG of the hippocampus, which may contribute to learning and memory aptitude.
Numerous exciting studies have focused on illuminating the molecular mechanisms that regulate NSC proliferation and survival in both developing and adult brains.
Many transcription factors and growth factors have been identified to control NSC proliferation and differentiation into various cell types. In recent years, epigenetic regulation of NSC development has also been revealed. Moreover, the niche that maintains NSCs has been realized. For example, the vascular system in the SVZ of adult brains has been shown to promote NSC proliferation.
Parallel to the growth of our understanding of NSCs at cellular and molecular levels, our attempt to utilize NSCs for repair of damaged neurons in neurodegeneration disorders and injuries has also made significant progress. Cultured NSCs have been transplanted into the brains of stroke models and into the spinal cord after injuries, and significant recoveries have been observed. Moreover, it has been found that ischemia promotes the endogenous NSCs to proliferate and migrate into damaged regions.
Taking the benefit of our knowledge of neurodevelopment and neural stem cell specification, embryonic stem cells (ESCs) have been used to produce NSCs and their progenies in cultures. The induced pluripotent stem cell (IPS) technology allows for NSCs to be generated directly from fibroblasts of patients with neurological disorders.
Excitingly, recent studies have shown that fibroblasts can be reprogrammed directly into neurons by skipping the IPS step. Consequently, we are no longer restricted to post-mortem samples of patients with neurological disorders. These new technologies allow scientists to reprogram patient fibroblasts into NSCs or neurons, identify abnormal gene regulations responsible for these disorders, and screen potential drugs for treatment. We still face many challenges, such as the difficulty of producing homogeneous neuronal populations for transplantation, and the strain in leading new neurons to form synaptic connections with exiting neurons. However, there is no doubt that NSCs are becoming a promising means for treatment of neurological diseases and injuries.
The publication of this book is timely. It contains the characterization of embryonic and adult neural stem cells in both invertebrates and vertebrates, and highlights the history and the most advanced discoveries in neural stem cells. This book provides the strategies and challenges of utilizing neural stem cells for therapy of neurological disorders and brain and spinal cord injuries.
I am honored to have had this opportunity to work with over 20 authors on this book.The expertise and scientific contribution from each author has enriched the depth and broadness of the book and I have learned a tremendous amount from each and every one of them. It has been a great pleasure to work with the staff members at InTech Open Access Publisher. In particular, I feel fortunate to have worked closely with Mr.Vedran Greblo, who has coordinated the publication of this book from the beginning to the end. It is his professional insight in publishing, and his patience and encouragement that has made this book possible.

Tao Sun

Weill Medical College of Cornell University


Part 1 Characterization of Neural Stem Cells .

  1 Neural Stem Cells from Mammalian Brain: Isolation Protocols and Maintenance Conditions 3  Jorge Oliver-De la Cruz and Angel Ayuso-Sacido

  2 Neurogenesis in Adult Hippocampus 31 Xinhua Zhang and Guohua Jin

  3 Cellular Organization of the Subventricular Zone in the Adult Human Brain:  A Niche of Neural Stem Cells 59  Oscar Gonzalez-Perez

  4 The Spinal Cord Neural Stem Cell Niche 71 Jean-Philippe Hugnot

  5 Development of New Monoclonal Antibodies for Immunocytochemical Characterization of Neural Stem and Differentiated Cells 93  Aavo-Valdur Mikelsaar, Alar Sünter, Peeter Toomik, Kalmer Karpson and Erkki Juronen

Part 2 Neural Stem Cells in Invertebrates .

  6 Formation of Nervous Systems and Neural Stem Cells in Ascidians 121  Kiyoshi Terakado

  7 Regeneration of Brain and Dopaminergic Neurons Utilizing Pluripotent Stem Cells:  Lessons from Planarians 141   Kaneyasu Nishimura, Yoshihisa Kitamura   and Kiyokazu Agata

Part 3 Regulation of Neural Stem Cell Development .

  8 -Secretase-Regulated Signaling Mechanisms: Notch and Amyloid Precursor Protein 161  Kohzo Nakayama, Hisashi Nagase, Chang-Sung Koh and Takeshi Ohkawara

  9 Role of Growth Factor Receptors in Neural Stem Cells Differentiation and Dopaminergic Neurons Generation 189  Lucía Calatrava, Rafael Gonzalo-Gobernado, Antonio S. Herranz, Diana Reimers, Maria J. Asensio, Cristina Miranda and Eulalia Bazán

  10 Musashi Proteins in Neural Stem/Progenitor Cells 205  Kenichi Horisawa and Hiroshi Yanagawa

 11 Active Expression of Retroelements in Neurons Differentiated from Adult Hippocampal Neural Stem Cells 223  Slawomir Antoszczyk, Kazuyuki Terashima, Masaki Warashina, Makoto Asashima   and Tomoko Kuwabara

  12 Noncoding RNAs in Neural Stem Cell Development 239 Shan Bian and Tao Sun

Part 4 Neural Stem Cells and Therapy .

  13 Neural Stem/Progenitor Cell Clones as Models for Neural Development and Transplantation 259  Hedong Li, He Zhao, Xiaoqiong Shu and Mei Jiang

  14 Endogenous Neural Stem/Progenitor Cells and Regenerative Responses to Brain Injury 285  Maria Dizon

  15 Neural Stem Cells: Exogenous and Endogenous Promising Therapies for Stroke 297  M. Guerra-Crespo, A.K. De la Herrán-Arita, A. Boronat-García, G. Maya-Espinosa, J.R. García-Montes, J.H. Fallon and R. Drucker-Colín

  16 Ischemia-Induced Neural Stem/Progenitor Cells Within the Post-Stroke Cortex in Adult Brains 343  Takayuki Nakagomi and Tomohiro Matsuyama

  17 Mesenchymal Stromal Cells and Neural Stem Cells Potential for Neural Repair in Spinal Cord Injury and Human Neurodegenerative Disorders 359  Dasa Cizkova, Norbert Zilka, Zuzana Kazmerova, Lucia Slovinska, Ivo Vanicky, Ivana Novotna-Grulova, Viera Cigankova, Milan Cizek and Michal Novak

  18 Assessing the Influence of Neuroinflammation on Neurogenesis: In Vitro Models Using Neural Stem Cells and Microglia as Valuable Research Tools 383  Bruno P. Carreira, Maria Inês Morte, Caetana M. Carvalho and Inês M. Araújo

  19 Immune System Modulation of Germinal and Parenchymal Neural Progenitor Cells in Physiological and Pathological Conditions 413  Chiara Rolando, Enrica Boda and Annalisa Buffo .

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Published by: Unknown - Monday, February 4, 2013


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