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This is an authoritative survey of the most recent scientific evidence showing how cyclosporin, FK-506, and their analogs - the neuroimmunophilins - evolved from being purely immunosuppressant "drugs" to neuroprotective "agents". The book focuses on recent preclinical evidence that demonstrates the neurotrophic/neuroprotective effects of immunosuppressants when administered alone or when combined with neural transplantation therapy in animal models of neurological disorders. It also discusses their efficacy and mechanisms of action in vitro and in vivo models of CNS disease, and provides laboratory studies with compelling clinical indications for Alzheimer's disease, Huntington's disease, stroke, traumatic brain injury, spinal cord injury, ALS, sciatic nerve injury, and drug addiction.
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Table of Contents

Part I: Immunosuppressants, Neurologic Disorders, and Neuroprotection Introduction: Immunosuppressants as Neuroprotective Agents Marcus F. Keep, Hiroyuki Uchino, and Eskil Elmer Part II: Immunosuppressants and Parkinson's Disease Cyclosporin-Mediated Amelioration of Degeneration of Dopaminergic Neurons in Experimental Models of Parkinsonism Norio Ogawa and Ken-ichi Tanaka Immunophilin Ligands and Dopamine Neurons: Specific Effects in Culture and In Vivo Lauren C. Costantini and Ole Isacson Effects of Neuroimmunophilin Ligands on Parkinson's Disease and Cognition Joseph P. Steiner, Douglas T. Ross, Hansjorg Sauer, Theresa Morrow, and Gregory S. Hamilton Improved Survival of Grafted Dopamine Neurons by Calcineurin Inhibitors Roger F. Castilho, Oskar Hansson, and Patrik Brundin Possible Mechanisms Underlying the Protective Action of Immunosuppressants Against Parkinson's Disease: The Mitochondrial Permeability Transition Pore Hypothesis L. V. P. Korlipara and A. H. V. Schapira Part III: Immunosuppressants and Other Age-Related Disorders Immunosuppressants and Alzheimer's Disease Mark P. Mattson Cyclosporin A Protects Striatal Neurons from Mitochondrial Dysfunction: Implications for Huntington's Disease Liza Leventhal and Jeffrey H. Kordower Part IV: Immunosuppressants, Stroke, and Traumatic Brain Injury Cyclosporin A Protects Mitochondria in an In Vitro Model of Hypoxia/Reperfusion Injury Vladimir Gogvadze and Christoph Richter Protective Effect of Cyclosporin A on Glial Activation and White Matter Alterations Induced by Chronic Cerebral Hypoperfusion Hideaki Wakita, Hidekazu Tomimoto, and Ichiro Akiguchi Blockade of Late-Onset Reduction of Muscarinic Acetylcholine Receptors by Immunosuppressants in Forebrain Ischemia Ken-ichi Tanaka, M. Asanuma, and NorioOgawa The Role of Immunophilins in Focal Cerebral Ischemia: Evidence of Neuroprotection by FK506 A. L. McGregor, P. A. Jones, J. F. McCarter, T. E. Allsopp, and J. Sharkey Immunosuppressants in Traumatic Brain Injury David O. Okonkwo and John T. Povlishock Part V: immunosuppressants and Spinal Cord Injury Inhibition of Lipid Peroxidation by Cyclosporin After Spinal Cord Injury in Rats Antonio Ibarra and Araceli Diaz-Ruiz Axonal Regeneration in Cyclosporin A-Treated Rats Submitted to Transverse Section of the Spinal Cord Guido Palladini and Brunella Caronti Part VI: Immunosuppressants and Sciatic Nerve Injury Neuroimmunophilin Ligands Accelerate and Promote Nerve Regeneration in the Rat Peripheral Nerve and Spinal Cord: Role of the Steroid Receptor-FKBP52 Complex Bruce G. Gold Neuroimmunophilin Ligands Stimulate Recovery of Injured Sciatic Nerves Joseph P. Steiner, Heather Valentine, Theresa Morrow, and Gregory Hamilton Part VII: Immunosuppressants and Other Disorders of the Central Nervous System Cyclosporin A Prolongs Survival of SOD1 Mutant Mice and Implicates Mitochondrial Permeability Transition in ALS Marcus F. Keep, Keith S. K. Fong, Katalin Csiszar, and Eskil Elmer Psychological Effects of Cyclosporine-A Shigeru Watanabe Index

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Forerword by Solomon H. Snyder

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