The wide range of contributions to this volume, from a detailed paper on the use of gene therapy in combination with hypothermia for the treatment of cerebral ischemia to a comprehensive poster describing the role of anesthetic agents in neurotoxicity during development and senescence, illustrate the scientific scope presented.
Contributions from clinical and basic science researchers from many disciplines address various approaches to providing neuroprotection. The clinical focus is on the complexity of neuroprotection, the need for understanding the time-course effects of hypoxia/ischemia, and the need for combinational and time-course applications of multiple therapies. New technologies are introduced for describing both the insult and the treatment necessary for neuroprotection, including gene expression assays (genomics) and gene therapy.
Several chapters are devoted to the examination of the predictive value of models for outcome measures in clinical ischemic stroke neuroprotective trials. The need to move from in vitro models to more predictive in vivo approaches with the use of pharmacokinetics is addressed. Other chapters emphasize the role of endogenous agents such as nitric oxide, melatonin, L-carnitine, and estrogens in acute and chronic neural injury and therapy.
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Part I: The Human Experience of Neuroprotection:.
1. Neuroprotection Trek - The Next Generation: The Measurement Is the Message: Russell J. Andrews.
2. Protective Effect of Neuromonitoring during Cardiac Surgery: Harvey L. Edmonds, Jr.
3. Neuropsychiatric Alterations in MDMA Users: Preliminary Findings: Ronald I. Herning, Warren Better, Kimberly Tate, And Jean L. Cadet.
4. Intraoperative Monitoring during Aneurysm Surgery as a Neuroprotective Activity with Reference to Evoked Potential and Microvascular Doppler Techniques: Karl E. Sanzenbacher.
5. Panel of Biomarkers Predicts Stroke: D T Laskowitz, R Blessing, J Floyd, W D White, And J R Lynch.
6. Evaluating Neuroprotective Agents in Coronary Artery Bypass Surgery: Stanton Newman.
7. Questions and Answers: Session I: The Human Experience of Neuroprotection.
Part II: Mechanisms of Neuroprotection (1):.
8. Delineating and Understanding Cerebellar Neuroprotective Pathways: Potential Implication for Protecting the Cortex: Xuan Wu, Xueying Jiang, Ann M. Marini, And Robert H. Lipsky.
9. A Role for Calpain in Optic Neuritis: M Kelly Guyton, Eric A. Sribnick, Swapan K. Ray, And Naren L. Banik.
10. Activation of Neuroprotective Pathways by Metabotropic Group I Glutamate Receptors: A Potential Target for Drug Discovery?: Andrius Baskys, Liwei Fang, And Ildar Bayazitov.
11. Antiapoptotic and Anti-inflammatory Mechanisms of Heat-Shock Protein Protection: Midori A. Yenari, Jialing Liu, Zhen Zheng, Zinaida S. Vexler, Jong Eun Lee, And Rona G. Giffard.
12. Neuroprotection by NGF in the PC12 In Vitro OGD Model: Involvement of Mitogen-Activated Protein Kinases and Gene Expression: Rinat Tabakman, Hao Jiang, Iris Shahar, Hadar Arien-Zakay, Robert A. Levine, And Philip Lazarovici.
13. Role of Peroxynitrite in Methamphetamine-Induced Dopaminergic Neurodegeneration and Neuroprotection by Antioxidants and Selective NOS Inhibitors: Syed F. Ali, Syed Z. Imam, And Yossef Itzhak.
14. Questions and Answers: Session II: Mechanisms of Neuroprotection (1).
Part III: Neuroprotection in Inflammation-Related Neurodegenerative Diseases:.
15. Microglial NADPH Oxidase Mediates Leucine Enkephalin Dopaminergic Neuroprotection: Liya Qin, Yuxin Liu, Xun Qian, Jau-Shyong Hong, And Michelle L. Block.
16. Effect of Neuroprotective Drugs on Gene Expression in G93A/SOD1 Mice: Sheila Ignacio, Dan H. Moore, Andrew P. Smith, And Nancy M. Lee.
17. Brain Response to Injury and Neurodegeneration: Endogenous Neuroprotective Signaling: Nicolas G. Bazan, Victor L. Marcheselli, And Kasie Cole-Edwards.
18. Early Effects of Modulating Nuclear Factor-B Activation on Traumatic Spinal Cord Injury in Rats: Octavio Jiménez-Garza, Javier Camacho, Antonio Ibarra, Angelina Martínez, And Gabriel Guízar-Sahagún.
19. Role of Inflammation in the Pathogenesis of Parkinson's Disease: Models, Mechanisms, and Therapeutic Interventions: Jau-Shyong Hong.
Part IV: Role of Carnitines and Other Agents in Neuroprotection:.
20. Mechanisms of Ischemic Neuroprotection by Acetyl-l-carnitine: Santina A. Zanelli, Nina J. Solenski, Robert E. Rosenthal, and Gary Fiskum.
21. Identification of Rat Hippocampal mRNAs Altered by the Mitochondrial Toxicant, 3-NPA: Beata D. Przybyla-Zawislak, Brett T. Thorn, Syed F. Ali, Richard A. Dennis, Antonino Amato, Ashraf Virmani, And Zbigniew K. Binienda.
22. l-Carnitine and Neuroprotection in the Animal Model of Mitochondrial Dysfunction: Zbigniew Binienda, Beata Przybyla-Zawislak, Ashraf Virmani, And Larry Schmued.
23. Effects of Metabolic Modifiers Such as Carnitines, Coenzyme Q10, and PUFAs against Different Forms of Neurotoxic Insults: Metabolic Inhibitors, MPTP, and Methamphetamine: Ashraf Virmani, Franco Gaetani, And Zbigniew Binienda.
24. Questions and Answers: Session IV: Role of Carnitines and Other Agents in Neuroprotection.
Part V: Neuroprotective Approaches and Models:.
25. The Antiapoptotic Actions of Mood Stabilizers: Molecular Mechanisms and Therapeutic Potentials: De-Maw Chuang.
26. Circulatory Arrest as a Model for Studies of Global Ischemic Injury and Neuroprotection: Lars Wiklund, Hari Shanker Sharma, and Samar Basu.
27. Possible Neuroprotective Mechanism of Human Neuroglobin: Keisuke Wakasugi, Chihiro Kitatsuji, And Isao Morishima.
28. The Impact of Aging, Dietary Restriction, and Glucocorticoids on ApoE Gene Expression in Rat Brain: S Ruzdijic, M Perovic, A Mladenovic, D Milanovic, L Rakic, S Petanceska, And S Kanazir.
29. Questions and Answers: Session V: Neuroprotective Approaches and Models.
Part VI: Neuroprotective Agents and Mechanisms.
30. Saposin C: Neuronal Effect and CNS Delivery by Liposomes: Zhengtao Chu, Ying Sun, Chia Yi Kuan, Gregory A. Grabowski, And Xiaoyang Qi.
31. Brain-Derived Neurotrophic Factor Is Neuroprotective against Human Immunodeficiency Virus-1 Envelope Proteins: Alessia Bachis And Italo Mocchetti.
32. Nicotinamide Modulates Energy Utilization and Improves Functional Recovery from Ischemia in the In Vitro Rabbit Retina: Diamond Tam, Majestic Tam, And Kenneth I. Maynard.
33. Mechanisms of Disease: Motoneuron Disease Aggravated by Transgenic Expression of a Functionally Modified AMPA Receptor Subunit: Rohini Kuner, Anthony J. Groom, Gerald Müller, Hans-Christian Kornau, Vanya Stefovska, Iris Bresink, Bettina Hartmann, Karsten Tschauner, Stefan Waibel, Albert C. Ludolph, Chrysanthy Ikonomidou, Peter H. Seeburg, And Lechoslaw Turski.
34. Questions and Answers: Session VI: Neuroprotective Agents and Mechanisms.
Part VII: The NMDA Receptor as a Target for Neurotoxicity and Neuroprotection:.
35. Potentially Neuroprotective and Therapeutic Properties of Nitrous Oxide and Xenon: Jacques H. Abraini, Hélène N. David, And Marc Lemaire.
36. Chronic Exposure to Nitrous Oxide Increases [3H]MK801 Binding in the Cerebral Cortex, but Not in the Hippocampus of Adult Mice: Natascha Sommer, Carmelo Romano, and Vesna Jevtovic-Todorovic.
37. Systems Biology/Systems Toxicology: Application to Developmental Neurotoxicology/Neuroprotection: William Slikker, Jr., Zengjun Xu, And Cheng Wang.
38. An Old Story with a New Twist: Do NMDAR1 mRNA Binding Proteins Regulate Expression of the NMDAR1 Receptor in the Presence of Alcohol?: Meena Kumari and Antje Anji.
39. Antioxidative Effect of Vitamin D3 on Zinc-Induced Oxidative Stress in CNS: Anya M. Y. Lin, K B Chen, And P L Chao.
40. Questions and Answers: Session VII: The NMDA Receptor as a Target for Neurotoxicity and Neuroprotection.
Part VIII: Mechanisms of Neuroprotection (2):.
41. Antioxidant Effects of N-Acetylserotonin: Possible Mechanisms and Clinical Implications: Gregory Oxenkrug.
42. Novel Neuroprotective Mechanism of Action of Rasagiline Is Associated with Its Propargyl Moiety: Interaction of Bcl-2 Family Members with PKC Pathway: Orly Weinreb, Tamar Amit, Orit Bar-Am, Orly Chillag-Talmor, and Moussa B. H. Youdim.
43. Gene Expression Profiling of Sporadic Parkinson's Disease Substantia Nigra Pars Compacta Reveals Impairment of Ubiquitin-Proteasome Subunits, SKP1A, Aldehyde Dehydrogenase, and Chaperone HSC-70: Silvia Mandel, Edna Grunblatt, Peter Riederer, Ninette Amariglio, Jasmine Jacob-Hirsch, Gideon Rechavi, and Moussa B. H. Youdim.
44. Neuronal Growth-Promoting And Inhibitory Cues In Neuroprotection And Neuroregeneration. By Stephen D. Skaper.
45. Immune-Modulating Effects of Melatonin, N-Acetylserotonin, and N-Acetyldopamine: Mary C. Perianayagam, Gregory F. Oxenkrug, and Bertrand L. Jaber.
46. N-Acetyldopamine Inhibits Rat Brain Lipid Peroxidation Induced by Lipopolysaccharide: Gregory F. Oxenkrug and Pura J. Requintina.
47. The In Vitro Effect of Estradiol and Testosterone on Iron-Induced Lipid Peroxidation in Rat Brain and Kidney Tissues: Pura J. Requintina and Gregory F. Oxenkrug.
48. Questions and Answers: Session VIII: Mechanisms of Neuroprotection (2).
Part IX: Sensitive Targets for Neurotoxicity and Neuroprotection:.
49. Neuroprotective Effects of Neurotrophins and Melanocortins in Spinal Cord Injury: An Experimental Study in the Rat Using Pharmacological and Morphological Approaches: Hari Shanker Sharma.
50. Neuroprotective Effects of Nitric Oxide Synthase Inhibitors in Spinal Cord Injury-Induced Pathophysiology and Motor Functions: An Experimental Study in the Rat: Hari Shanker Sharma, Rajendra D. Badgaiyan, Per Alm, S Mohanty, and Lars Wiklund.
51. Acrylamide Stimulates Glutamine Uptake in Fischer 344 Rat Astrocytes by a Mechanism Involving Upregulation of the Amino Acid Transport System N: Qi Wu, Marta Sidoryk, Lysette Mutkus, Magdalena Zielinska, Jan Albrecht, and Michael Aschner.
52. Effects of Acrylamide on Primary Neonatal Rat Astrocyte Functions: Michael Aschner, Qi Wu, and Marvin A. Friedman.
53. Neuroprotection by Platelet-Activating Factor Antagonism: Xiaohua Tian and Nicolas G. Bazan.
54. Questions and Answers: Session IX: Sensitive Targets for Neurotoxicity and Neuroprotection.
Part X: Novel Approaches to Neuroprotection:.
55. Expression of Prostaglandin E2 Synthases in Mouse Postnatal Cortical Neurons: Valentina Echeverria, David L. Greenberg, and Sylvain Doré.
56. Novel Neuroprotective Tripeptides and Dipeptides: Alan I. Faden, Susan M. Knoblach, Vilen A. Movsesyan, Paul M. Lea, Iv, and Ibolja Cernak.
57. Cocaine Induces a Differential Dose-Dependent Alteration in the Expression Profile of Immediate Early Genes, Transcription Factors, and Caspases in PC12 Cells: A Possible Mechanism of Neurotoxic Damage in Cocaine Addiction: Syed Z. Imam, Helen M. Duhart, John T. Skinner, and Syed F. Ali.
58. Neuroprotection in the PNS: Erythropoietin and Immunophilin Ligands: Ahmet Höke And Sanjay C. Keswani.
59. Questions and Answers: Session X: Novel Approaches to Neuroprotection.
Part XI: Workshop PBPK/PD Models for Developing Humans: Risk Assessment Strategies and Research Recommendations:.
60. Improving Predictive Modeling in Pediatric Drug Development: Pharmacokinetics, Pharmacodynamics, and Mechanistic Modeling: William Slikker, Jr., John F. Young, Richard A. Corley, David C. Dorman, Rory B. Conolly, Thomas B. Knudsen, Brian L. Erstad, Richard H. Luecke, Elaine M. Faustman, Charles Timchalk, and Donald R. Mattison.
Index of Contributors
Russell J. Andrews NASA Ames Research Center, Moffet Field, California.
Bruce Trembly Veterans Affairs Medical Center, Togus, Maine.