Author : Peter Egerton Batchelor
Publisher :
Page : 568 pages
File Size : 20,30 MB
Release : 2000
Category : Central nervous system
ISBN :
Author : Gunnar Heiko Dirk Poplawski
Publisher :
Page : 279 pages
File Size : 22,61 MB
Release : 2014
Category :
ISBN : 9781321059946
The regenerative capacity of central nervous system (CNS) axons after injury is severely impaired compared to axons of the peripheral nervous system (PNS). We hypothesized that mechanisms both intrinsic and extrinsic to the neuron influence the ability of CNS axons to regenerate. To investigate this hypothesis we explored two model systems. In the first model system, we identified a regeneration transcriptome in injured corticospinal motor neurons that is associated with enhanced central axon regeneration after spinal cord injury. The genetic mechanisms identified in this model include cAMP-Erk-CREB, Huntingtin, NFE2L2, ephrin and semaphorin signaling, and provide a dataset for potential therapeutic intervention to improve axonal regeneration in vivo after spinal cord injury. In the second model, we tested the hypothesis that glial cells of the peripheral nerve, Schwann cells, are an essential mechanism contributing to central axonal regeneration after "conditioning" lesions, wherein injury to the peripheral branch of a dorsal root ganglion sensory neuron enhances regeneration of the central branch of the sensory neuron. The gene encoding Low-density lipoprotein Receptor-related Protein-1 (LRP1) was conditionally deleted in Schwann cells, impairing the survival and function of Schwann cells after injury; animals with Schwann cell-specific deletion of LRP1 exhibited a significant reduction in axon regeneration in vitro and a trend towards central sensory axon regeneration after conditioning lesions, confirming that glial cells exhibit an essential but partial role in supporting axonal regeneration. Overall, these studies identify novel molecular and cellular mechanisms that influence central axon regeneration, and suggest therapeutic approaches to improve neural repair after CNS injury.
Author : Billy You Bun Lau
Publisher :
Page : 264 pages
File Size : 31,17 MB
Release : 2012
Category :
ISBN :
Spinal cord injury induces anatomical plasticity throughout the nervous system, including distant locations in the brain. Several types of injury-induced plasticity have been identified, such as neurite sprouting, axon regeneration and synaptic remodeling. However, the molecular mechanisms involved in anatomical plasticity after injury are unclear, as is the extent to which injury-induced plasticity in the brain is conserved across vertebrate lineages. Here, I used lampreys to identify the molecular mechanisms in mediating anatomical plasticity, because lampreys undergo anatomical plasticity and functional recovery after a complete spinal cord transection. Due to their robust roles in neurite outgrowth during neuronal development, I examined synapsin and synaptotagmin for their potential involvement in anatomical plasticity after injury. I found increased synapsin I mRNA throughout the lamprey brain as well as increased protein levels of synapsin I, phospho-synapsin (Ser 9) and synaptotagmin in the lamprey hindbrain after injury, suggestive of anatomical plasticity. Anatomical plasticity was confirmed at the ultrastructural level, where I found increased neurite density in the lamprey hindbrain after injury. Other molecular mechanisms that promote anatomical plasticity have been previously identified, such as cyclic AMP (cAMP). However, the cellular mechanisms and the molecular targets of cAMP in mediating anatomical plasticity are unclear. My investigation of cAMP revealed that cAMP enhanced the number of regenerated axons beyond the lesion site in lampreys after injury. For the first time in a spinal cord injury model, I found cAMP prevented the death of axotomized neurons that normally have a high tendency to die after injury. In addition, cAMP promoted more regenerating axons to re-grow in straighter paths rather than turning rostrally towards the brain stem. At the molecular level, I found cAMP increased synaptotagmin protein level at the regenerating axon tips, suggestive of enhanced axon elongation. Taken together, my results show that neurite sprouting in the brain and the cAMP-enhanced axon regeneration are conserved responses in vertebrates after spinal cord injury. In addition, my results suggest that at least some developmental pathways are activated during injury-induced and cAMP-enhanced anatomical plasticity. Further understanding of these pathways will provide insights for improving recovery after spinal cord injury.
Author : Mathias Bähr
Publisher : Springer Science & Business Media
Page : 264 pages
File Size : 14,40 MB
Release : 2007-03-06
Category : Medical
ISBN : 0387301283
Brain Repair, addresses all relevant issues underlying the mechanisms of brain damage, brain plasticity and post-traumatic reorganisation after CNS lesions. This book is divided the three major sections that follow; cellular and molecular basis of brain repair, plasticity and reorganisation of neural networks, and experimental therapy strategies. Brain Repair is written by high profile, international experts who describe in detail the newest results from basic research and highlight new model systems, techniques and therapy approaches. Based on a careful analysis of the cellular and molecular reaction patterns of the CNS to lesions, the contributions cover possibilities for endogenous reorganisation and repair as well as exciting new therapies emerging from basic research, some of which have already been introduced into the clinics. Thus, this book is unique in bridging the gap between basic and clinical research. It will be a valuable tool for all students, researchers and clinicians interested in understanding the brain's capacity to cope with lesions and interested in learning about emerging new therapy concepts.
Author :
Publisher : Academic Press
Page : 233 pages
File Size : 23,17 MB
Release : 2012-12-31
Category : Science
ISBN : 0123983223
Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews and thematic volumes that focus on recent progress in a specific area of neurobiology research. This volume reviews existing theories and current research surrounding Axon Growth and Regeneration. - Leading authors review state-of-the-art in their field of investigation and provide their views and perspectives for future research - Chapters are extensively referenced to provide readers with a comprehensive list of resources on the topics covered - All chapters include comprehensive background information and are written in a clear form that is also accessible to the non-specialist
Author : Luis B. Tovar-y-Romo
Publisher : Frontiers Media SA
Page : 255 pages
File Size : 26,78 MB
Release : 2021-10-13
Category : Science
ISBN : 2889714705
Author : Lars P. Klimaschewski
Publisher : Springer Nature
Page : 195 pages
File Size : 11,64 MB
Release :
Category :
ISBN : 366268053X
Author : Audrey N. Kusiak
Publisher : Elsevier Inc. Chapters
Page : 79 pages
File Size : 43,31 MB
Release : 2013-01-10
Category : Medical
ISBN : 0128077921
Once thought to be rigidly wired, the spinal cord now is understood to display significant plastic properties, which are manifest as both physiological and structural alterations in response to changes in patterns of use, disuse, and damage. Activity-dependent increases in responsiveness of spinal cord circuits are now thought to underlie or contribute importantly to the hyperalgesia that often follows neurological injuries, the physical therapy-induced improvement in walking and running seen in patients with stroke and spinal cord injury, skill acquisition in normal children, and several other phenomena. Physiological mechanisms underlying spinal cord plasticity include denervation supersensitivity, long-term potentiation, long-term depression, and habituation. Anatomical plasticity seen in the spinal cord after partial injuries includes collateral sprouting of spared axons in response to injury of neighboring axons, and dendritic remodeling in response to loss of regionally segregated synaptic inputs. A form of neuroplasticity that is seen in the peripheral nerves and in the spinal cord of some cold-blooded animals, but not in the central nervous system of birds or mammals, is axon regeneration. It is often difficult to distinguish between regeneration of injured axons and collateral sprouting of neighboring uninjured axons, but the distinction could be very important, especially in the case of complete spinal cord injuries. Several instances of treatment-induced axonal changes that were originally thought to indicate regeneration have turned out to be collateral sprouting. There is reason to suspect that the molecular mechanisms that underlie these two phenomena are different, and, if so, therapeutic approaches to enhancing them may also prove to be very different.
Author : Christine C. Stichel-Gunkel
Publisher : Springer Science & Business Media
Page : 126 pages
File Size : 14,61 MB
Release : 2012-12-06
Category : Medical
ISBN : 3642607810
Since the pioneering studies of Ramon y Cajal the inability of lesioned adult CNS axons to regenerate has been well established. During the past years advancements in molecular, cellular and biochemical knowledge have provided new insights into the extrinsic mechanims underlying regeneration failure. The rapid progress in this field has already led to the development of new concepts for therapeutic manipulations. This book provides a comprehensive overview of structural and molecular changes induced by an invasive CNS lesion and their involvements in regeneration processes. Moreover, it demonstrates the strong growth-promoting actitivies of implanted glial cells. The data is discussed in relation to current knowledge on the mechanisms of axonal degeneration and regeneration and in terms of their relevance for the development of novel therapeutic strategies.
Author : Santiago Ramón y Cajal
Publisher : History of Neuroscience
Page : 977 pages
File Size : 39,61 MB
Release : 1991
Category : Nervous system
ISBN : 0195065166
This book is a reprint of an English translation of Cajal's original work, with abundant notes and commentaries by the editor. This text describes Cajal's fundamental contributions to neuroscience, which continue to be important today. It accurately details Cajal's ideas and data, and providesreaders with the opportunity to learn what Cajal thought about his research career and the significance of his observations. Excerpts from Tello's memorial lectures also provide a contemporary view of Cajal's work.
