Axonal Regeneration in the Mammalian Central Nervous System

1 Hypotheses Concerned with Regeneration in the Mammalian Central Nervous System.- 1.1 Introduction.- 1.2 Histopathological Response to Trauma.- 1.2.1 PNS of Mammals.- 1.2.2 CNS of Submammalian Vertebrates.- 1.2.3 CNS of Mammalian Vertebrates.- 1.3 Successful Regeneration of Some Neurons in the Mammalian CNS.- 1.4 Hypotheses to Explain the Limited Regenerative Capacity of CNS Neurons.- 1.4.1 Intrinsic Inability of CNS Neurons to Regenerate?.- 1.4.2 Formation of Inappropriate Synapses.- 1.4.3 Autoimmune Inhibition of Regenerative Attempts.- 1.4.4 Progressive Necrosis at the Lesion Site and the Formation of Cystic Cavities.- 1.4.5 Proliferation of Fibroblasts, Neuroglial and Endothelial Cells at the Lesion Site.- 1.4.6 Absence of Schwann Cells in the CNS as Guides for Regenerating Axons.- 1.4.7 Necessity of an Ependymal - Mesenchymal Interaction.- 1.4.8 Incompatibility Between the Neuronal Processes and the Non-neuronal Cells of the CNS.- 1.4.9 Inhibition of Axonal Growth by Post-injury Myelin Breakdown Products.- 1.4.10 A Lack of Periaxonal Vascular Permeability.- 1.4.11 An Absence of Requisite Growth Factors.- 1.4.12 Ineffective Somal Response by CNS Neurons to Axotomy.- 1.4.13 Necessity of Recent or Continued Neurogenesis.- 2 In Vivo Experimental Approaches to Hypotheses Concerned with Regeneration in the Mammalian CNS.- 2.1 Introduction.- 2.2 Submammalian Vertebrates.- 2.2.1 Inappropriate Synaptogenesis.- 2.2.2 Non-neuronal Environment.- 2.2.3 Somal Response.- 2.2.4 Vascular Permeability.- 2.2.5 Necessity of Recent or Continued Neurogenesis.- 2.3 Developmental Events in Mammals.- 2.3.1 Non-neuronal Environment.- 2.3.2 Necessity of Recent or Continued Neurogenesis.- 2.3.3 Vascular Permeability.- 2.4 Morphological and Biochemical Assessment of Regeneration in Mammals.- 2.4.1 Inappropriate Synaptogenesis.- 2.4.2 Necrosis and Cyst Formation.- 2.4.3 Neuroglial Scar Tissue.- 2.4.4 Auto-immune Hypothesis.- 2.4.5 A Role for Schwann Cells?.- 2.4.6 Myelin Breakdown Products.- 2.4.7 A Need for Vascular Permeability?.- 2.4.8 Somal Response.- 2.5 The Use of Transplants.- 2.5.1 Peripheral Nerve Transplants.- 2.5.2 Transplants of Fetal Mammalian CNS Tissue.- 2.5.3 Transplantation Studies of Amphibian and Mammalian Glial Scar Tissue.- 2.5.4 Schwann Cell Transplants to the PNS and CNS.- 2.5.5 Transplants of Non-nervous Tissue.- 2.5.6 Transplants of Autonomic Ganglia to the CNS.- 2.5.7 Transplants of Non-cellular Conduits.- 2.6 Pharmacological Approaches.- 2.6.1 Piromen.- 2.6.2 Adrenocorticotrophic Hormone.- 2.6.3 Enzyme Treatment.- 2.6.4 Tri-iodothyronine and L-thyroxine.- 2.6.5 Immunosuppressants.- 2.6.6 Dimethyl Sulphoxide.- 2.6.7 Puromycin.- 2.6.8 Gangliosides.- 2.6.9 Nerve Growth Factor.- 2.6.10 Cytosine Arabinoside.- 2.7 Conclusions.- 3 In Vitro Experimental Approaches to Hypotheses Concerned with Regeneration in the Mammalian CNS.- 3.1 Introduction.- 3.2 The Role of the Microenvironment - Neuronotrophic Factors.- 3.2.1 NGF and Other NTFs.- 3.2.2 In Vitro-Conditioned Media.- 3.2.3 In Vivo-Derived PNS and CNS Wound Fluid.- 3.2.4 Fibroblast Growth Factors.- 3.2.5 Hormonal NTFs.- 3.3 The Role of the Microenvironment - The Substrate and Substrate-Bound Neurite Promoting Factors.- 3.3.1 Mechanism of Neurite Growth.- 3.3.2 Role of the Substrate in Neurite Elongation.- 3.3.3 Substrate-Bound Neurite Promoting Factors.- 3.3.4 Basal Lamina Constituents.- 3.4 The Role of the Microenvironment - Humoral Neurite-Promoting Factors.- 3.4.1 NGF and NGF-Like Molecules.- 3.4.2 NPFs in Conditioned Media.- 3.4.3 NPFs and CNS Wounds.- 3.4.4 Fibroblast Growth Factors.- 3.4.5 Hormonal NPFs.- 3.4.6 Gangliosides.- 3.5 The Role of the Microenvironment - The Non-neuronal Cells.- 3.5.1 Transplants of Non-neuronal Cultured Cells.- 3.5.2 Non-neuronal Cells - Differential Substrate Adhesiveness in the Support of Neurite Elongation.- 3.5.3 In Vivo-Derived CNS Wound Fluid and Glial Mitogens.- 3.5.4 Effect of Non-neuronal Cell Proliferation on Neurite Outgrowth.- 4 Conclusions.- References.