Although there are over 400,000 people each year in the United States alone who suffer from traumatic injury to the central nervous system (CNS), no phar­ macological treatment is currently available. Considering the enormity of the problem in terms of human tragedy as well as the economic burden to families and societies alike, it is surprising that so little effort is being made to develop treatments for these disorders. Although no one can become inured to the victims of brain or spinal cord injuries, one reason that insufficient time and effort have been devoted to research on recovery is that it is a generally held medical belief that nervous system injuries are simply not amenable to treatment. At best, current therapies are aimed at providing symptomatic relief or focus on re­ habilitative measures and the teaching of alternative behavioral strategies to help patients cope with their impairments, with only marginal results in many cases. Only within the last decade have neuroscientists begun to make serious inroads into understanding and examining the inherent "plasticity" found in the adult CNS. Ten years or so ago, very few researchers or clinicians would have thought that damaged central neurons could sprout new terminals or that intact nerve fibers in a damaged pathway could proliferate to replace inputs from neurons that died as a result of injury.

1. Therapeutic Approaches in Subjects with Brain Lesions.- 1. Introduction.- 2. Developmental, Degenerative, and Regenerative Factors Related to Brain Plasticity.- 3. Mechanisms of Cell Damage Linked to Ischemia.- 4. Drugs Used to Treat Ischemic Cell Damage.- 5. Management of Medical and Neurological Complications.- 6. Requirements in the Design of a Clinical Trial.- 7. Individualization of Drug Therapy.- 8. The GABA Technique of Reversible Brain Dysfunction.- References.- 2. Arachidonic Acid Metabolites and Membrane Lipid Changes in Central Nervous System Injury.- 1. Introduction.- 2. Membrane Lipid Changes in CNS Injury.- 2.1. Direct Membrane Effects.- 2.2. Eicosanoid Production.- 3. Pharmacological Intervention.- 3.1. Direct Membrane Protection.- 3.2. Eicosanoid Blockade.- 4. Research in Progress.- 5. Conclusion.- References.- 3. Experimental Spinal Cord Injury: Strategies for Acute and Chronic Intervention Based on Anatomic, Physiological, and Behavioral Studies.- 1. Introduction and a Brief History of Spinal Cord Injury Research.- 2. Current Methods for Lesion Production.- 2.1. Impact Injuries.- 2.2. Slow(er) Compression Injuries.- 3. The Time Course of Events following Injury.- 3.1. The Acute Phase and the Concept of a Progressive Lesion.- 3.2. The Chronic Phase: Potential Reorganization and Rehabilitation.- 4. The Features of the Lesion.- 4.1. At the Impact Site.- 4.2. The Distributed Nature of the Lesion.- 5. Assessing Behavioral and Neurological Recovery.- 6. Examples of Attempts at Pharmacological Intervention.- 6.1. In the Acute Phase.- 6.2. In the Chronic Phase.- 6.3. Adjuncts to Pharmacological Treatment.- 7. Studies Using the Ohio State Impaction Device.- 7.1. The Ohio State Feedback-Controlled Impactor.- 7.2. Production of Lesions with Predictable Outcomes.- 7.3. The Role of Ionic Ca2+ in the Acute Phase.- 8. Future Strategies for Pharmacological Intervention.- 8.1. In the Acute Phase.- 8.2. In the Chronic Phase.- 9. Summary and Conclusions.- References.- 4. Serotonin Antagonists Reduce Central Nervous System Ischemic Damage.- 1. Introduction.- 2. Review of the Effects of Serotonin in Stroke.- 3. New Methods for the Study of CNS Ischemia.- 3.1. Rabbit Spinal Cord Ischemia Model.- 3.2. Microsphere Embolic Stroke Model.- 4. Biochemical Studies of the Effects of Serotonin in CNS Ischemia.- 5. Pharmacological Studies of the Effects of Serotonin Antagonists and Agonists in CNS Ischemia.- 6. Microsphere Studies of the Effects of Serotonin Antagonists on Stroke.- References.- 5. Opiate Antagonists in CNS Injury.- 1. Introduction.- 2. Opiate Antagonists.- 3. Rationale for Use of Opiate Antagonists in CNS Injury.- 3.1. Opiate Antagonists in the Treatment of Spinal Cord Injury.- 3.2. Opiate Antagonists and Traumatic Brain Injury.- 4. Role of Specific Opioids and Opiate Receptors in CNS Injury.- 5. Opiate Antagonists in CNS Injury: Clinical Studies.- 6. Future Directions.- References.- 6. Adaptive Changes in Central Dopaminergic Neurons after Injury: Effects of Drugs.- 1. Introduction.- 2. Anatomy and Function of Mesencephalic Dopaminergic Neurons.- 3. Compensatory Changes in Transmitter Release.- 4. Pharmacological Stimulation of DA Synthesis and Release in Dopaminergic Neurons Surviving Partial Nigrostriatal Lesions.- 5. Compensatory Changes in Postsynaptic Receptor Sensitivity.- References.- 7. Catecholamines and Recovery of Function after Brain Damage.- 1. Historical Background.- 1.1. Tactile Placing.- 1.2. Visual Cliff.- 1.3. Hemiplegic Rat Model.- 1.4. Norepinephrine and the Importance of Experience.- 1.5. Hemiplegic Cat Model.- 1.6. Binocular Vision.- 2. Theoretical Bases.- 2.1. Morphological Changes.- 2.2. Vicariation.- 2.3. Behavioral Substitution.- 2.4. Cerebral Blood Flow and Cholinergic System.- 2.5. Diaschisis, RFD, and Metabolic Studies.- 3. Recent Data.- 3.1. Cytochrome Oxidase.- 3.2. Idazoxan.- 3.3. Locus Coeruleus and Cerebellum.- 3.4. Phentermine and Phenylpropanolamine.- 3.5. Transplants.- 3.6. Cortical Contusion.- 3.7. Clinical Data.- 3.8. Drug Contraindications.- 4. Future Directions.- 4.1. Mechanisms.- 4.2. Optimizing Therapy.- References.- 8. Ganglioside Involvement in Membrane-Mediated Transfer of Trophic Information: Relationship to GM1 Effects following CNS Injury.- 1. Introduction.- 1.1. Neuronotrophic Activity after Injury.- 1.2. Trophic Effects and Exogenous Factors.- 1.3. Trophic Effects and Membrane Constituents.- 2. Evidence for Ganglioside Involvement in the Biotransduction of Membrane-Mediated Information.- 2.1. Chemical Diversity of the Gangliosides.- 2.2. Tissue Distribution and Cellular Localization.- 2.3. Membrane Organization.- 3. Evidence for Ganglioside Involvement in Neuronal Cell Responsiveness to Neuronotrophic Factors.- 3.1. Studies in Normal Neuronal Development and "Accidents of Nature".- 3.2. Studies Utilizing Neuroblastoma Cells.- 3.3. Studies Utilizing Primary PNS Neurons and PC12 Cells.- 3.4. Studies Utilizing Primary CNS Neurons.- 4. GM1 Effects in Vivo: Possible Relationship with Neuronotrophic Factors.- References.- 9. Anatomic Mechanisms whereby Ganglioside Treatment Induces Brain Repair: What Do We Really Know?.- 1. Introduction.- 2. Regeneration and Sprouting after Brain Injury.- 2.1. Gangliosides in Development and Peripheral Nerve Regeneration.- 2.2. Sprouting in Adulthood.- 2.3. Sprouting in Development.- 2.4. Conclusions on Sprouting.- 3. Preventing Secondary Degeneration after Brain Injury.- 3.1. Degeneration in Adulthood.- 3.2. Degeneration in Development.- 4. Other Mechanisms.- 4.1. Denervation Supersensitivity.- 4.2. Synaptic Efficiency.- 5. Discussion.- 6. Recommendations for Future Research.- References.- 10. Gangliosides and Functional Recovery from Brain Injury.- 1. Introduction.- 2. Behavioral Recovery following Damage to the Septohippocampal System.- 3. Behavioral Recovery following Damage or Denervation of Cortical Structures.- 3.1. Recovery after Lesions to the Cholinergic Forebrain Nuclei.- 3.2. Recovery after Cortical Lesions.- 3.3. Recovery after Ischemia.- 4. Behavioral Recovery following Nigrostriatal Damage.- 4.1. Early Studies on Recovery following Nigrostriatal Damage.- 4.2. Later Studies on Recovery after Nigrostriatal Damage.- 4.3. Recent Data on Recovery after Nigrostriatal Damage.- 4.4. Recent Data on Recovery after Bilateral Lesions of the Caudate Nucleus.- 5. General Discussion and Conclusions.- References.- 11. Acute Ganglioside Effects Limit CNS Injury: Functional and Biochemical Consequences.- 1. Long-Term Ganglioside Effects: Increased Plasticity.- 2. Acute Gan…