Axonal Regeneration In The Central Nervous System
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Axonal Regeneration in the Central Nervous System
Summarizing a review of research into factors that regulate, stimulate, and prevent regeneration in the central nervous system (CNS), this comprehensive reference progresses further into answering and resolving neuron capacity for axon regeneration in the mammalian CNS. Axonal Regeneration in the Central Nervous System analyzes axonal regeneration, reinnervation, and functional recovery in lower vertebrates examines the correlation between developmental age and the ability to regenerate considers mammalian neuron responses at the cell body, site of injury, and in the distal nerve, including apoptic cell death, and inflammatory and glial responses to injury reviews genomic responses to axotomy with a comparative description of transcribed genes from successfully regenerating neurons and neurons incapable of regrowth discusses how growing axons may induce the expression of genes in glia/Schwann cells following axotomy and regeneration describes the use of gene therapy to deliver trophic and survival factors to injured neurons explores the hospitable environments of the peripheral nerve, olfactory ensheathing cells, and fetal cell transplants for regeneration discusses results from applications of fetal CNS tissue to human spinal cord injuries and much more!
Mechanisms of Axonal Regeneration in the Central Nervous System
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.
Axonal Regeneration in the Mammalian Central Nervous System
Author: Dorothy E. Oorschot
language: en
Publisher: Springer Science & Business Media
Release Date: 2012-12-06
This state-of-the-art review links the experimental data into a cohesive and critical account of CNS regeneration. Research findings are discussed in terms of their relevance to one (or more) of thirteen hypotheses concerned with regeneration in the mammalian CNS. Research findings reviewed include: regeneration in developing mammals and in submammalian vertebrates, the use of transplants and/or pharmacological treatments, in vitro studies on neurotrophic and neurite promoting factors and their potential relevance to CNS regeneration in vivo, and in vitro studies on the types of glial cells that may be responsible for enhancing or suppressing axonal re-growth.